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Biomedical subjects

S Esposito

Publications and source records attributed to S Esposito.

At least 55 records · Page 3Linked to original sources

Efficacy of high-dose interferon in combination with ribavirin in patients with chronic hepatitis C resistant to interferon alone.

OBJECTIVE: Interferon combined with ribavirin has efficacy in the treatment of patients with chronic hepatitis C virus (HCV) infection. However, its utility in patients who have not responded to prior interferon therapy is not clear. Furthermore, the effect of using an increased dose of interferon in combination with ribavirin in patients with chronic hepatitis C resistant to conventional doses of interferon is not known. The aim of our study was to evaluate the effect of high-dose interferon in combination with ribavirin on the efficacy of treating patients with chronic hepatitis C resistant to interferon monotherapy in a large multicenter trial. METHODS: We randomized 154 patients with chronic hepatitis C who failed to achieve a sustained response with prior interferon therapy to receive either 3 or 5 MU of interferon alpha-2b and ribavirin (1000-1200 mg/day) for 12 months. There were 119 patients who had not responded and 35 who initially responded but relapsed after prior interferon monotherapy. Serum HCV RNA levels were measured at entry, 6, and 12 months of treatment and at the end of a 6-month follow-up period. RESULTS: The mean age of the subjects was 47 yr (range 28-68 yr), and 110 (71.4%) were men. One hundred thirty-two patients (86%) had HCV genotype 1, whereas 21 (14%) had cirrhosis. Eighty-one subjects (53%) were randomized to receive 3 MU of interferon alpha-2b. Fifteen of 35 relapse subjects (43%) and 12 of 119 prior nonresponder entrants (10%) achieved a sustained virological response to the 12-month course of treatment. Overall, 11 of 81 patients (14%) receiving 3 MU, and 16 of 73 patients (22%) receiving 5 MU of interferon maintained an undetectable HCV RNA level after cessation of therapy. The difference in sustained response rates between the two interferon dosage groups did not reach statistical significance (p = 0.09). However, among the nonresponder patients alone, there was an increased sustained response in the high-dose interferon group compared with the standard interferon dose group (15.5% vs 4.9%, p = 0.055). Twenty-six patients discontinued therapy before 6 months, including 10 patients (12.3%) in the 3-MU and 16 patients (21.9%) in the 5-MU groups (p = 0.17). CONCLUSIONS: Sustained virological response to combined interferon alpha-2b and ribavirin was significantly higher in relapse patients than those who did not respond to prior interferon monotherapy. Although, when all treated patients were analyzed, there was no significant difference in sustained response between subjects receiving 3 and 5 MU of interferon, among the prior nonresponder patients, treatment with 5 MU of interferon with ribavirin resulted in a slightly increased response compared with treatment with the standard interferon dosage. The tolerability of the treatment regimens was comparable.

Adult↗

Long-term pertussis-specific immunity after primary vaccination with a combined diphtheria, tetanus, tricomponent acellular pertussis, and hepatitis B vaccine in comparison with that after natural infection.

The aim of this study was to compare pertussis-specific humoral and cellular immunity in children 5 years after a primary vaccination with a combined diphtheria, tetanus, tricomponent acellular pertussis, and hepatitis B vaccine (DTaP-HBV; InfanrixHepB; SmithKline Beecham) with immunity after natural infection. The subjects were 38 children aged 5 to 6 years who received DTaP-HBV at 3, 5, and 11 months of life and 21 subjects of similar ages and sex who acquired pertussis in the first year of life. Immunoglobulin G (IgG) antibody titers against Bordetella pertussis antigens, peripheral blood mononuclear cell-specific proliferation, and the secretion of cytokines were evaluated. After 5 years, only a small proportion of vaccinated and infected children had significant specific concentrations of IgG in serum against all three B. pertussis antigens, and T-cell responses persisted in a minority of subjects. A preferential type 1 cytokine response with the secretion of gamma interferon was observed in the pertussis group, whereas a type 2 skewed response was observed in the vaccinated children; however, the quantitative differences in the cytokines produced by DTaP-HBV and natural infection were minimal. In conclusion, our results show that the immune responses induced by primary pertussis vaccination are qualitatively and quantitatively similar to those seen in children who recovered from natural infection and highlight the need for booster immunization with pertussis vaccines in order to maintain adequate levels of a specific immune response to B. pertussis.

Antibodies, Bacterial↗

Treatment of lower respiratory tract infections in Italy: the role of outpatient parenteral antibiotic therapy.

The use of outpatient parenteral antibiotic therapy (OPAT) has enjoyed substantial success in Italy, where patients generally believe that treatment at home is better than in the hospital. Intramuscular administration, which is commonplace in Italy, facilitates OPAT, requiring minimal training and circumventing intravenous access problems. The Italian OPAT model is a general practice-based model, but a team approach is used in the presence of severe disease, such as HIV. Seven centers in Italy are participating in the International OPAT Outcomes Registry, and have enrolled about 200 patients over 8 months. Eighty patients (40%) were treated for lower respiratory tract infections (60 pneumonia, 20 bronchitis). Most pneumonia patients had concomitant disease, including chronic heart disease, HIV and cancer. The most frequently used therapy was ceftriaxone, which permits once-daily convenience due to its prolonged half-life. Antibiotics were administered intramuscularly in more than 50% of cases. Clinical outcome was excellent, and patient and physician satisfaction was high.

Anti-Bacterial Agents↗

Immune system and surgical site infection.

It is well known that altered host defenses in general can play a significant role in the development of infection in any patient but their role becomes even more important in surgical patients where infections are the result of individual risk factors associated with the patient and other specific factors associated with the surgery itself. Thus all possible factors that can help modify the immune response should be taken into account in order to intervene, whenever possible, with therapies based on defined abnormalities to reduce the rate of post-surgical infections. Many factors associated with the patient have been clearly identified as responsible for a decreased immune response: old age, concomitant diseases (diabetes, renal and liver failure, solid and hematologic neoplasias, malnutrition, autoimmune diseases, AIDS) and concomitant therapies (corticosteroid, cytotoxic agents). Old age can affect both humoral and cell-mediated immune responses. Chronic diseases can be responsible for a reduced primary response or depression of delayed hypersensitivity reactions (renal failure, neoplasias) or changes in leukocyte function (diabetes, leukemia, lymphomas). Malnutrition frequently accompanies diseases such as cancer, chronic and acute pancreatitis, inflammatory bowel diseases. Deficiencies in important vitamins and minerals (B6, A, folate, biotin, riboflavin...) can alter significantly the leukocyte function and immune response. Finally, there appears to be innate immune-suppression following any form of injury which is correlated with its magnitude and can affect any aspect of immunity. This has been well studied both in burn and surgical trauma. Alteration of phagocytosis, opsonization and chemotaxis are typically affected in burns, whereas surgical stress can include some reduction of cell mediated immunity. The best approach today to minimizing post-surgical infections is probably, besides use of antibiotic prophylaxis, to reduce the surgical trauma which consequently reduces the stress response and immune-suppression and to optimize the immune response by maintaining homeostasis through nutritional support.

Animals↗

Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with pneumonia. Mowgli Study Group.

The most common clinical signs, host responses and radiographic patterns were studied in 203 Italian children hospitalized for community-acquired pneumonia in order to clarify the role of clinical and radiological characteristics in the diagnosis of Mycoplasma pneumoniae and/or Chlamydia pneumoniae infections. Antibody measurements in paired sera and polymerase chain reaction on nasopharyngeal aspirates were used to establish the diagnoses of acute M. pneumoniae and C. pneumoniae infection, and the aetiologic data were correlated with the clinical, laboratory and radiographic data obtained on admission. No significant association was observed between evidence of M. pneumoniae and/or C. pneumoniae infection and periods of episode during the year, mean age of the study subjects, individual symptoms, physical findings or laboratory test results. Furthermore, no significant correlation was observed in relation to the radiological findings and M. pneumoniae and/or C. pneumoniae infection. This study shows that neither clinical findings nor laboratory parameters distinguished Mycoplasma pneumoniae and/or Chlamydia pneumoniae infection in children with pneumonia. Radiological findings also have a limited capacity to differentiate aetiologic agents. The priorities for future research include the development of rapid, easily accessible and cost-effective diagnostic tests useful for each episode of pneumonia in children.

Acute Disease↗

Asthma in children: are chlamydia or mycoplasma involved?

Asthma aetiology is complex, involving interactions between genetic susceptibility, allergen exposure and external aggravating factors such as air pollution, smoking and respiratory tract infections. Available evidence supports a role for acute Chlaymdia pneumoniae or Mycoplasma pneumoniae respiratory tract infection as a trigger for 5 to 30% of wheezing episodes and asthma exacerbations. It also appears that acute infections with C. pneumoniae and M. pneumoniae can initiate asthma in some previously asymptomatic patients; however, the quantitative role for these atypical bacteria as asthma initiators is unknown at the present time. Whether chronic infections with these agents play an important role in persistent asthma symptoms and/or to asthma severity is unclear and additional information should be acquired before definite conclusions can be reached. Improvement in asthma symptoms after antimicrobial therapy active against C. pneumoniae and M. pneumoniae has been observed. In some studies C. pneumoniae seems to be more important for asthma pathogenesis and exacerbations than M. pneumoniae; in other reports the role of M. pneumoniae appears to be more significant. However, a number of questions remain unanswered. Carefully controlled randomised trials are clearly warranted to determine whether infection with atypical bacteria is really associated with asthma and to define the appropriate role of antimicrobial treatment.

Acute Disease↗

Lipoma of the heart: a case report.

Lipomas of the heart are rare (only 0.5% according to the Armed Forces Institute of Pathology series) and their diagnosis is often difficult because they are asymptomatic; in fact, in contrast to lipomatous hypertrophy, lipomas are usually found on the epicardial surfaces of the atria or ventricles. In our case, the lipoma was located in both atria and was attached to the interatrial septum involving also the right pulmonary veins, the inferior vena cava and the right phrenic nerve. At histology, the tumor was composed only of mature adipose tissue with entrapped myocytes and vessels. The combination of computed tomography and transesophageal echocardiography allowed a precise diagnosis in terms of the localization and tissue characterization of the tumor.

Echocardiography, Transesophageal↗

[Role of flowmetric analysis and of color-Doppler ultrasonography with contrast media in the different phases and follow-up of Graves' disease].

PURPOSE: The objectives of this study were: 1) to evaluate the role of color-Doppler ultrasonography (CDU) assessment of thyroid vascularity, measuring the peak systolic velocity (PSV) at the level of the inferior thyroid artery, and the intrathyroid vascularization in Graves' diseas; 2) to evaluate the role of contrast agent administration in predicting the relapse of hyperthyroidism or the biological activity of the disease after withdrawal of antithyroid drugs. PATIENTS AND METHOD: The study included 74 Graves' patients (59 F/ 15 M; mean age 45 years; range 23-71). Graves' disease was diagnosed according to the usual clinical and laboratory criteria. On the basis of the clinical and biochemical findings we divided Graves' patients into 4 different groups. Treatment was continued for at least 12 months, CDU examination was carried out after discontinuing therapy. Eight patients showed a relapse of hyperthyroidism within 5 months after suspension of therapy. In all cases the evaluation of intraparenchymal vascularization and PSV at the level of the inferior thyroid artery in basal conditions was followed by administration of contrast agent (Levovist, 300 mg/ml), with slow infusion (<2 ml/min) to avoid blooming artifact. Intraparenchymal vascularization was classified into 4 patterns according to Vitti et al. RESULTS: The value of the peak systolic velocity (PSV) at the level of the inferior thyroid artery was the best predictor of relapse. A value higher than 40 cm/sec was present in all the patients that showed relapse and only in two patients with stable remission. Administration of contrast agent is important to evaluate the biological activity of the disease. In the 5 patients exhibiting slightly increased vascularization after contrast agent administration we could assume the clinico-pathological recovery. CONCLUSIONS: CDU study of thyroid vascularization, based on the measurement of PSV at the level of the inferior thyroid artery and on the response to contrast agent administration is useful to distinguish three groups of patients: A) PSV >40 cm/sec with pattern III for at least 10 minutes from the beginning of the contrast agent administration (High risk of relapse); B) PSV <40 cm/sec with pattern II or III after contrast agent administration (Biological activity of the disease-Thyroiditis); C) PSV <40 cm/sec with Pattern I after contrast agent administration (Poor biological activity of the disease-recovery).

Adult↗

[Outpatient parenteral antibiotic treatment: the Italian model].

Though constrained by the lack of standard criteria for patient selection and well defined therapeutic protocols, the Italian model of OPAT is characterized by the home treatment of infections also of moderate severity, chiefly of the lower respiratory tract by means of broad spectrum antibiotics (chiefly beta-lactams) administered intramuscularly. The selection of patient for OPAT remains an individual decision of GPs based on the severity of infection, concomitant diseases, age of the patient, reliability of patients and family, environ- mental and social factors. Such a model has gained broad consensus over the years from patients for different cultural reasons: first, the willingness of patients to participate in the OPAT programmes, second, the concept that home is better than hospital even when you are ill and, third, the fact that parenteral drugs are perceived as more effective than oral ones, probably in contrast with the culture and traditions of other countries (especially northern Europe) where hospitals are still considered the only proper site of care and intramuscular administration is regarded as almost unnatural. No private or insurance reimbursement based OPAT structure exists up to now in Italy or is go. ing to be developed. The main problems in Italy now seems to be: -to define clear protocols and easy criteria for selection of patients enable to OPAT, -to improve what existing by creating and/or qualifying new professionals involved with in- and outpatients (OPAT, early discharge,medical care for special populations.).

Administration, Oral↗

[Role of parenteral cephalosporins for outpatients treatment of infections].

OPAT (Outpatient Parenteral Antibiotic Therapy) arose in the early 1980s in the USA and later in many other countries from the primary consideration that outpatient treatment is more cost-effective than hospitalisation. Currently, several thousand patients undergo OPAT programmes all over the world and several different bacterial infections are included in the list of treatable diseases, especially those requiring long-term parenteral treatment such as osteomyelitis and soft tissue infections. All injectable antibiotics are suitable for OPAT according to their microbiological spectrum, although clearly some pharmacological properties make one antibiotic more preferable than another. Beta-lactams represent more than half of the antibiotic world market and two-thirds of them are cephalosporins. Such a widespread use of cephalosporins is certainly due to their wide antibacterial spectrum and good tolerability. Among third-generation cephalosporins, covering the majority of micro-organisms responsible for community-acquired infections, ceftriaxone is the only one with an 8-hour half-life, thereby permitting a single daily dose, which represents a great advantage when undertaking an OPAT programme. Analysis of antibiotic consumption used for OPAT therapies, based on data collected from the International OPAT Registry project, with the participation of many countries (USA, Canada, Britain, Argentina, etc.) including Italy, shows that ceftriaxone is the most widely used antibiotic for home therapy, clearly due to the above-mentioned properties.

Ambulatory Care↗

[Immigration and sexually transmitted diseases: risk factors, prevention and health education].

Assessment of behaviour at risk of HIV-infection and other Sexually Transmitted Diseases (STD) in high-risk subjects, such as illegal immigrants is the first step for successful prevention measures. In order to assess knowledge of AIDS, STDs, risk behaviour and condom use, a sexual behaviour questionnaire was administered to all illegal immigrants living in the Domitia area (north-west of naples) and coming to our ambulatory for several pathologies. The following risk markers identified were: low level of knowledge concerning HIV and STD transmission and prevention, multiple sexual partners, casual sex, low frequencies of condom use, drugs and alcohol use. Therefore prevention campaigns should include educational activities concerning AIDS and STD transmission and prevention, and condom promotion. Particular attention should be given to improve access to STD services that provide treatment and counselling. Moreover, commercial sex workers require counselling at each visit, screening and treatment.

Adult↗

[Infectious diseases].

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Acquired Immunodeficiency Syndrome↗

Heparan N-sulfatase gene: two novel mutations and transient expression of 15 defects.

Sanfilippo syndrome type A or mucopolysaccharidosis IIIA (MPS IIIA) results from the deficiency of the enzyme heparan N-sulfatase (NS, EC 3.10.1.1), required for the degradation of heparan sulfate. Molecular defects of 24 Italian MPS IIIA patients were recently reported by our group. We report here two novel mutations: 1040insT and Q365X and the expression studies on 15 of the identified defects. Transient expression of COS cells by cDNA mutagenized to correspond to heparan N-sulfatase mutations Y40N, A44T, 166delG, G122R, P128L, L146P, R150Q, D179N, R182C, R206P, P227R, 1040insT, 1093insG, E369K, R377C did not yield active enzyme, demonstrating the deleterious nature of the mutations. Western blot analysis and metabolic labeling experiments revealed, for cells transfected with wild-type enzyme, a precursor 62-kDa form and a mature 56-kDa form. Western blot resulted, for 11 mutations, in the presence of both forms, indicating a normal maturation of the mutant enzyme. Western blot, metabolic labeling and immunofluorescence experiments suggested, for mutations 166delG, L146P, 1040insT and 1093insG, an increased degradation of the mutant enzymes.

Animals↗

Determinants and prognostic value of ischemic necrosis in early biopsies following heart transplant.

To evaluate the impact of early ischemic necrosis (IN) on the early and late outcome of heart transplantation, we reviewed our 11-year experience. Between January 1988 and June 1999, 207 heart transplants were performed in 205 patients (174 male and 31 female). Criteria for donor and recipient selection, and protocols for postoperative immunosuppression and rejection monitoring have remained unchanged over this period. Three different cardioplegic solutions were employed in graft preservation: St. Thomas Hospital solution in the earliest 31 cases (15%), University of Wisconsin solution in 96 cases (46.4%), and Celsior solution in the last 80 cases (38.6%). All patients who underwent at least one endomyocardial biopsy (176 patients) were divided into two groups according to the findings of IN within the early 3 postoperative months (group A, 49 patients with IN; group B, 127 patients without IN). The following variables were estimated in each group: donor and recipient age, ischemic time, type of cardioplegia, late mortality for cardiac causes, incidence of grade >2 rejection within the first 6 postoperative months, late incidence of grade >2 rejection, late incidence of NYHA class >II. No significant difference was found in any parameter between the two groups, except for the type of cardioplegic solution. A significantly higher incidence of ischemic necrosis in hearts preserved with St. Thomas solution was found (P < 0.001). Although pathology findings show that extracellular solutions carried a higher risk of early IN, no associated significant impairment in terms of late survival and event-free rate was observed in recipients with early IN.

Adolescent↗

Evaluation and use of plant biodiversity for food and pharmaceuticals.

Many epidemiological studies have shown the importance of fruit and vegetables in the human diet so as to prevent the onset of cardiovascular disease and several forms of cancer. The use for food and pharmaceuticals of two of the most widely grown and genetically well-known species in the world, the tomato and the potato, is reviewed. Tomatoes are important sources of vitamin C, potassium, folic acid and carotenoids such as lycopene and beta-carotene. It has been demonstrated that lycopene has anti-oxidant properties and interferes with the growth of cancerous cells. At the Department of Agronomy and Plant Genetics in Portici, interesting results have been obtained with the constitution of stable tomato hybrids having a high content of lycopene and vitamin C. Many of the parental lines used in constituting the hybrids come from interspecific crosses. Potato is also very important in the human diet for its content of high quality proteins, mineral salts and vitamins and it has many medicinal properties. The use of diploid wild species to transfer traits such as high content of vitamin C, mineral salts and high quality proteins into the cultivated potato through ploidy manipulation is discussed.

Carotenoids↗