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Biomedical subjects

M Palla

Publications and source records attributed to M Palla.

18 recordsLinked to original sources

Aerosolized interferon-alpha treatment in patients with multi-drug-resistant pulmonary tuberculosis.

Multi-drug-resistant tuberculosis (MDR-TB) has emerged as an obstacle to the control of tuberculosis. Recent data however, suggest that interferon-(IFN)-gamma and IFN-alpha may improve disease evolution in subjects affected with pulmonary tuberculosis caused by multi-resistant (IFN-gamma) and sensitive (IFN-alpha) strains. The mechanisms involved are not known, even though it has been reported that IFN-gamma-secreting CD4+ Th cells may possess antitubercular effects. In addition, IFN-alpha can induce IFN-gamma secretion by CD4+ Th cells, and both types of IFN may stimulate macrophage activities. The aim of this study was to explore the possibility that aerosolized IFN-alpha, administered concomitantly with conventional antitubercular chemotherapy, may improve the course of pulmonary tuberculosis. After six months of directly observed therapy (DOT), seven patients who were non-responders to a second line antitubercular therapy were given an IFN-alpha aerosol (3 MU, three times a week) for two months as adjunctive therapy. All strains were resistant to at least two first-line drugs. After IFN-alpha administration, the patients were followed up for a further six months with the same DOT. Sputum samples were collected monthly during the study period, with the exception of the IFN-alpha administration period, when the observations were performed weekly. High resolution computed tomography (HRCT) chest scans were performed before and after IFN-alpha inhalations. The analysis of the results showed that the mean number of Mycobacterium tuberculosis (Mt) had remained statistically unchanged (p = 0.80) during the first 6 months of DOT. During the following 2 months of IFN-alpha administration, 5 patients became negative (p = 0.02). After the end of treatment a progressive increase in Mt number was observed (p = 0. 02). Sputum cultures remained positive for all patients throughout the study period, although a significant decrease (p = 0.02) in the colony number per culture was observed after adjunctive treatment with IFN-alpha. After stopping administration of IFN-alpha, a significant increase (p = 0.03) in the colony number per culture was noted as well as in Mt numbers. HRCT scans were slightly improved in all patients. These preliminary data suggest that aerosolized IFN-alpha may be a promising adjunctive therapy for patients with MDR-TB. Optimal doses and schedules however, require further studies.

Adult↗

Collagen-based new bioartificial polymeric materials.

Bioartificial polymeric materials, based on blends of biological and synthetic polymers, have been proposed as new materials for applications in the biomedical field. They should usefully combine the biocompatibility of the biological component with the physical and mechanical properties of the synthetic component. Blends of collagen with either poly(vinyl alcohol) or poly(acrylic acid) have been prepared by mixing aqueous solutions of the two polymers. Differential scanning calorimetry and dynamic mechanical thermal analysis has been carried out to investigate the miscibility properties of the polymers and the mechanical behaviour of the blends.

Acrylic Resins↗

The activation of human plasma prekallikrein as a hemocompatibility test for biomaterials. II. Contact activation by EVAL and EVAL-SMA copolymers.

The activation of human plasma prekallikrein (PKK) to kallikrein (KK), induced by the contact of blood with foreign materials, is a useful in vitro hemocompatibility test. Kallikrein is easily detected by its reaction with the chromogenic substrate H-D-Pro-Phe-Arg-pNA, which releases p-nitroaniline, revealed by its absorption at 405 nm. This test, which was already carried out by evaluating PKK activation by the 'end-point' method, has been carried out in this work by the more accurate 'initial velocity' method, i.e. by evaluating the activation from the initial rates of the KK-substrate reaction. The tests were carried out on the following materials: borosilicate glass (as a high-activation reference material), silicone (as a low-activation reference material), the commercial biomaterial Cardiothane 51, three graft copolymers synthesized in our laboratory by reacting ethylene-vinyl alcohol copolymer (EVAL) with styrene-maleic anhydride copolymer (SMA), and EVAL itself. A mathematical treatment based on a simple kinetic model has been used for a first-approximation evaluation of the PKK-activating power of the materials tested. The quite low activating power of the EVAL-SMA copolymers, which are easily processable into water-permeable hollow fibers, suggests the possibility of their use in blood dialyzers.

Amino Acid Sequence↗

Microneutralization as a reference method for selection of the cut-off of an enzyme-linked immunosorbent assay for detection of IgG antibody to human cytomegalovirus.

In view of developing an enzyme-linked immunosorbent assay (ELISA) for the determination of IgG antibody to human cytomegalovirus, a rapid microneutralization (Nt) assay was used to test five positive standard sera containing increasing amounts of specific antibody and a negative standard serum. The standard serum containing the minimal amount of detectable Nt antibody was selected as a cut-off standard for the ELISA test. Following preliminary testing on previously characterized sera which gave expected results, the ELISA assay was tested in the field on 992 sera from blood donors. In parallel, sera were tested by Nt and complement fixation (CF). ELISA detected 82 negative and 910 positive sera. Nt gave concordant result except for two ELISA-negative sera, which showed Nt antibody titers of 1:10. The absorbance value of these two sera was just below that of the cut-off. Thus, for ELISA, the sensitivity was 99.8% (910/912) and specificity 100% (80/80). CF gave results concordant with ELISA and Nt, except for 23 sera (2 ELISA- and Nt-negative, and 21 ELISA- and Nt-positive) showing anticomplementary activity. Quantitation of specific ELISA antibody was achieved by interpolation from a calibation curve. Nt appears to be the reference test to establish the ELISA cut-off.

Antibodies, Viral↗

Development of small-diameter vascular prostheses which release bioactive agents.

A porous, distensible, tubular membrane which incorporates albumin and basic Fibroblast Growth Factor (bFGF), and is potentially utilizable as a bioactive small-diameter vascular prosthesis, was fabricated by a combined spraying, phase-inversion technique using a suspension of albumin and bFGF into a polyetherurethane-urea (Biomer) solution in dimethylacetamide (DMA). Scanning electron microscopy showed a material with an open-cell trabecular structure and small particles of albumin and/or bFGF entrapped in the bulk of the polyurethane trabeculae. The material released albumin and bFGF at an approximately constant rate for at least 2 weeks. The bFGF initially incorporated in the polymer remained biologically active as shown by in-vitro proliferation of human endothelial cells.

Albumins↗

HBeAg/anti-HBe determination with a new monoclonal immunoradiometric assay.

The performance of two assays for the HBeAg/anti-HBe system associated with hepatitis B virus infection, using monoclonal (EBK-Sorin) and polyclonal (HBe-Abbott) antibodies, has been compared. The results on a random population (1,000 samples) demonstrated for the monoclonal reagent a higher sensitivity, without any loss in specificity, and with the further advantage of the use of lower radioactivity levels. The proportion of positives and negatives obtained with the two kits was found to remain unchanged in the case of HBeAg, while a markedly larger percentage of positives (7% higher) was detected for anti-HBe using the monoclonal antibodies.

Antibodies, Monoclonal↗

HBsAg/IgM complexes in serum of HBsAg carriers: partial characterization and clinical significance.

HBsAg bound to IgM was detected in serum of HBsAg carriers with a radioimmunoassay based on selective absorption of the immunoglobulin on a solid phase coated with antiserum to human IgM. High titers of HBsAg/IgM were found in sera with the highest HBsAg binding capacity of polymerized human serum albumin (poly-HSA) and of C1q. These findings and the inhibition of HBsAg/IgM reaction by addition of purified poly-HSA suggest that the IgM component of the complex might bind to poly-HSA fixed on to HBsAg particles and possibly represent antibody to the modified plasma protein. HBsAg/IgM was detected in 95 (87%) patients with acute HBsAg positive hepatitis during the acute phase of infection and persisted after the fourth week only in patients who developed chronic liver disease. HBsAg/IgM were detected in one out of 15 carriers of the HBsAg with superimposed Non B hepatitis. HBsAg/IgM were also present in 76% to 100% of sera from chronic carriers without any relation to the extent of viral replication and to presence of severity of liver disease. Persistence of HBsAg/IgM in patients with acute hepatitis B may provide a useful tool to predict transition of HBV infection to chronicity.

Acute Disease↗

Complexes between HBsAg and IgM in serum of patients with acute hepatitis.

HBsAg bound to IgM was measured in the serum of HBsAg carriers with acute hepatitis using a radioimmunoassay based on selective absorption of IgM on solid phase coated with antiserum to human IgM. HBsAg/IgM was detected in 94 (100%) patients with acute type B hepatitis during the acute phase of infection and persisted after the fourth week only in 13 of them, who developed chronic liver disease. HBsAg/IgM was detected only in 1 patient out of 15 carriers of the HBsAg with superimposed non-B hepatitis. No activity was found in serum of 20 patients with acute HBsAg-negative hepatitis. The nature of the IgM component of the complex is uncertain, however, blocking experiments of the HBsAg/IgM reaction with polymerized human albumin suggest that the IgM component of the complex might represent antibody to the denatured protein. Persistent HBsAg/IgM complex detection in patients with acute type B hepatitis provides a useful tool to predict transition of HBV infection to chronicity. Its absence in patients with acute HBsAg-positive hepatitis is indicative of non-B hepatitis in chronic carriers of the HBsAg.

Acute Disease↗

Complexes of hepatitis B surface antigen and immunoglobulin M in the sera of patients with hepatitis B virus infection.

Hepatitis B surface antigen (HBsAg) bound to immunoglobulin M (IgM) was detected in sera of HBsAg carriers by a radioimmunoassay based on selective absorption of the immunoglobulin on a solid phase coated with antiserum to human IgM. Isopycnic banding and rate-zonal sedimentation have shown that the reaction is related to particulate forms of the HBsAg complexed with IgM. The binding of IgM possibly occurred because of a selective affinity of these molecules to the surface of HBsAg particles. HBsAg/IgM was found transiently in 24 of 25 (96%) patients with acute self-limited hepatitis B and persistently in 6 of 25 patients whose acute hepatitis B progressed to chronicity. It was also found in 20 of 39 (51%) chronic HBsAg carriers with inactive and asymptomatic infection. The HBsAg/IgM phenomenon is not dependent on replication of hepatitis B virions; its persistence in patients with acute hepatitis B may provide complementary evidence of transition of the infection to chronicity.

Animals↗

Acquired neutrophil myeloperoxidase deficiency: an indicator of subclinical activation of blood coagulation?

Using an automated cytochemical analyzer used for routine differential counts, we have been able to demonstrate acquired myeloperoxidase deficiency in 102 patients at our institution. Clinical and laboratory data on these patients showed a high incidence of diabetes mellitus (25.5%) and thrombotic diseases (24.5%), as well as a strikingly constant hyperfibrinogenemia (mean = 635 mg/100 ml; range = 360-1015 mg/100 ml). In 4 additional acute leukemia patients in complete remission, a close time correlation was noted between acquired MPO deficiency, diffuse intravascular coagulation and relapse. These findings indicate the importance of the relationships between neutrophil granulocytes and blood coagulation, and suggest that similar changes in neutrophil MPO activity may represent an early morphological indicator of subclinical activation of blood coagulation.

Adolescent↗

Persistence of circulating HBsAg/IgM complexes in acute viral hepatitis, type B: an early marker of chronic evolution.

Serial serum samples from 110 patients with acute viral hepatitis type B were tested for HBsAg/IgM complexes by a newly developed solid-phase radioimmunoassay. In 102 patients the infection resolved and they recovered from the disease. In these patients, HBsAg/IgM complexes were either absent from the outset of disappeared from serum within four weeks of admission, long before HBsAg had cleared or serum alanine aminotransferase had returned to normal, 8 patients progressed to chronic HBsAg carrier state and chronic liver disease. In these patients, HBsAg/IgM complexes were detectable in the serum on admission, and never disappeared. These results indicate that persistence of circulating complexes containing HBsAg and IgM after the early phase of acute viral hepatitis type B is a predictor of disease chronicity. As early as the fifth week of illness those in whom chronic liver disease developed could be distinguished from those who recovered.

Adolescent↗

A solid-phase enzyme immunoassay (EIA) for detection of HBeAg and anti-HBe.

A sensitive, reproducible and easily performed enzyme immunoassay (EIA) based on a sandwich technique is described for serological detection of HBeAg and anti-HBe. EIA appears to be 600 times more sensitive than immunodiffusion and counterimmunoelectrophoresis and its performance compares well with available radioimmunoassays.

Antibodies, Viral↗

Radioimmunoassay for the detection of HBeAg and anti-HBe.

We describe a solid-phase radioimmunoassay, based on the "sandwich" principle, using anti-HBe1/anti-HBe2 containing IgG precoated to polystirene beads as the solid-phase, and 125I-anti-HBE as labelled antibody for the detection of HBeAg and a two steps competitive procedure for the detection of anti-HBe. Comparison of titre obtained by ID and RIA or reference sera containing HBeAg and anti-HBe revealed that RIA is about 200 fold more sensitive than ID in detecting both HBeAg and anti-HBe. Moreover an increase in the detection rate of HBeAg from 5.9% (ID) to 15% (RIA) and of anti-HBe from 47.8% (ID) to 74.2% (RIA) and consequently a reduction of the frequency of negative samples for both HBeAg and anti-HBe from 46.3% (ID) to 10.8% (RIA) was determined by testing sera from HBsAg asymptomatic carriers. With regard to specificity, the frequency of presumptive HBeAg positive samples not confirmed was of 1 out of 29 (3.4%). Technical improvements of sensitivity and specificity of the described RIA are under development.

Antibodies, Viral↗