Search PubMed⌕ Search

Biomedical subjects

M Galli

Publications and source records attributed to M Galli.

At least 127 records · Page 7Linked to original sources
PubMed1997

Risk of Kaposi's sarcoma-associated herpes virus transmission from donor allografts among Italian posttransplant Kaposi's sarcoma patients.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a newly discovered herpes virus found in all forms of Kaposi's sarcoma (KS) including KS among immunosuppressed transplant patients. It is unknown whether this virus is transmitted by organ transplantation or is reactivated during immunosuppression among those patients infected before transplantation. To investigate the risk of KSHV transmission during organ transplantation, we conducted a case-control study of transplant recipients with and without KS matched to their respective donors. Sera were collected at time of transplantation and tested in a randomized and blinded fashion using four KSHV serologic assays testing for antibodies to both latent and lytic phase antigens. Ten (91%) of 11 organ recipients who developed KS were seropositive prior to transplantation by one or more of the assays compared with two (12%) of 17 control organ recipients (OR = 75, 95% CI = 4.7, 3500). KS cases were more likely to have been born in southern Italy where KS is endemic than the recipient controls or either donor group. Only four (36%) of 11 donors to case patients and three (18%) of 17 donors to control patients were seropositive (P = .38, two-tailed Fisher's exact test). KSHV transmission could not be ruled out for the single KS patient seronegative at transplantation and clear evidence for organ-related transmission was found for another KS patient outside of the case-control study. Antibodies to KSHV are detectable in the sera from most transplant recipients before initiation of immunosuppressive treatment suggesting that KS among immunosuppressed transplant patients is primarily due to virus reactivation. KSHV transmission, however, from an infected allograft can occur, and our study reports the first documented case of person-to-person transmission of KSHV.

Adult↗
PubMed1997

High prevalence of false-negative anti-HTLV type I/II enzyme-linked immunosorbent assay results in HIV type 1-positive patients.

A high frequency of false-negative anti-HTLV-I/II ELISA results has been reported by several authors. To verify the possible underestimate of the prevalence of HTLV-II infection in subjects infected by HIV-1, we used the PCR to investigate the presence of HTLV DNA in peripheral blood mononuclear cells (PBMCs) collected from a group of 67 HIV-1-positive anti-HTLV-I/II ELISA-negative individuals; the study population included 31 patients with HIV-1-related peripheral neuropathy (PN), 15 with non-Hodgkin lymphoma (NHL), and 23 without PN or NHL. Two subjects had both PN and NHL. All of the patients who were positive at PCR were investigated for the presence of serum anti-HTLV-I/II antibodies by means of Western blot (WB). Eighteen (26.9%) of the 67 anti-HTLV-I/II ELISA-negative patients had HTLV DNA in their PBMCs and WB-detectable serum antibodies directed against one or more HTLV antigens. The individuals affected by predominantly sensory polyneuropathy (PSP) had a significantly higher prevalence of HTLV DNA than the others. All of the patients in whom HTLV-I/HTLV-II discrimination was successful had HTLV-II, with the exception of one patient who was infected by HTLV-I. The present study confirms the possibility of HTLV infection in the absence of ELISA-detectable serum anti-HTLV-I/II antibodies, especially in the particular setting of HIV-1-infected individuals. Moreover, the fact that the prevalence of HTLV DNA was significantly higher in the subjects affected by predominantly sensory polyneuropathy further supports the possibility of an association between HIV-1-related PSP and HTLV-II.

Adult↗
PubMed1997

Comparable biological and molecular determinants in HIV type 1-infected long-term nonprogressors and recently infected individuals.

Human immunodeficiency virus type 1 (HIV-1) isolability, rate of replication, phenotype, plasma viremia, and specific intracellular transcripts were cross-sectionally analyzed in 61 HIV-1-seropositive individuals to evaluate the correlations between the virological and molecular correlates of protection and progression in different clinical subsets: recently infected subjects (RIs), long-term nonprogressors (LTNPs), late progressors (LPs), and typical progressors (TPs). Comparison of the major virological and molecular features of HIV-1 infection has defined distinct profiles for different subsets of patients. LTNPs or RIs, as well as LPs or TPs, exhibited similar titers of coculture p24 antigen; the differences between the former and the latter were statistically significant at all the time points tested (p = 0.0001; 0.0003 and 0.0001). Whereas LTNPs and RIs revealed comparable low levels of indexes of viral replication, LPs and TPs showed higher genome and mRNA copy numbers (p = 0.0004 and p = 0.0008, respectively). We demonstrated close biological and molecular similarities between RIs and LTNPs on the one hand, and LPs and TPs on the other. In LTNPs both viral biological properties and viral load are important determinants of the course of the disease.

CD4 Lymphocyte Count↗
PubMed1997

Patterns of in vitro anti-human immunodeficiency virus type 1 antibody production in long-term nonprogressors.

With the aim of evaluating the specific pattern of in vitro antibody production (IVAP) in human immunodeficiency virus type 1 (HIV-1)-infected long-term non-progressors (LTNPs), we tested 20 subjects who had remained asymptomatic for more than 8 years with a CD4+ cell count higher than 500/microliter and 59 patients at different stages of HIV-1 infection as controls. In cell cultures, IVAP was detected in 14 out of 20 LTNPs (70%), in 5 out of 6 recent seroconverters (83%), and in all the other control patients. Anti-p24 antibody production was significantly lower in LTNPs than in asymptomatic patients with a more recent infection. Recent seroconverters and patients with AIDS did not produce anti-p24 antibodies (P = 0.02). Anti-gp160 antibodies were produced by peripheral blood mononuclear cells from LTNPs in 12/20 cases. CD4+ cell count was significantly higher in IVAP-negative than in IVAP-positive LTNPs (P = 0.013), while the viral load was not significantly different. Specific anti-HIV-1 antibody production did not seem to be a correlate of long-term nonprogression.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Italian multicentre study of didanosine compassionate use in advanced HIV infection. Italian BMS-906 Study Group.

The aim of the present study, a multicentre trial of didanosine (ddI) compassionate use, was to identify factors associated with a better outcome in patients given ddI monotherapy. Enrolled were 1047 HIV-positive patients intolerant of and/or unresponsive to zidovudine (ZDV) therapy, with CD4+ cell counts of < 200/microliter or AIDS. Didanosine was given at a dose of 250 mg b.i.d. (patients > or = 60 kg) or 167 mg b.i.d. (patients < 60 kg). Clinical examinations and laboratory tests were performed every two months. Endpoints included death, the occurrence of a new AIDS-defining disease, or permanent discontinuation of ddI for a severe adverse event. At entry, the median CD41 cell count was 47/microliter and the median duration of prior ZDV treatment 19 months; 446 patients (43%) were classified as having AIDS. Severe toxicity occurred in 143 subjects (14%); the frequency of pancreatitis was very low (0.2%). The benefit in terms of CD4+ cell counts was greater for patients whose counts exceeded 100/microliter at entry and remained at this level until month 12 in those patients still receiving treatment. Death and/or new AIDS-defining events were observed in 374 cases (36%) over a median follow-up of eight months. AIDS dementia was observed in 11 patients (1%). Multivariate analysis of survival without disease progression showed that the factors associated with a worse outcome include the severity of immunodepression, a diagnosis of AIDS at entry, and a history of both intolerance of and clinical resistance to ZDV. Surprisingly, the patients who had received previous prolonged treatment with ZDV had a better outcome. In conclusion, severely immunodepressed patients previously administered long-term monotherapy may receive a short-term benefit from being switched to another antiretroviral drug.

AIDS Dementia Complex↗
PubMed1997

ECG-manifest and ECG-silent dipyridamole technetium-99m sestamibi SPET perfusion defects in patients with ischaemic heart disease.

At dipyridamole myocardial scintigraphy, perfusion defects are seldom backed up by significant ECG changes. This would suggest myocardial blood flow heterogeneity, rather than true ischaemia, as the cause of the scintigraphic abnormalities. Electrocardiographic surface mapping has been documented to be more accurate than standard 12-lead ECG in the detection of provoked ischaemia. Thus, to investigate the relationship between ECG changes and perfusion abnormalities, body surface maps were recorded during dipyridamole infusion in 55 subjects (11 normals and 44 patients with ischaemic heart disease) undergoing dipyridamole technetium-99m sestamibi single-photon emission tomography (SPET). All had a normal resting ECG. The extent and severity of the sestamibi defect were quantified. New negative areas in the isointegral maps and rest-dipyridamole map differences >2 SD from normal limits were considered abnormal. After dipyridamole in normals, neither perfusion defects nor >/=1 mm ST segment depression on 12-lead ECG nor new negative areas in isointegral maps occurred. In patients, dipyridamole induced new perfusion defects in 35 (80%) but ST segment depression in only 18 (41%, P<0.001). Of the 35 patients with perfusion defects, 17 (49%, group 1) showed ST segment depression, while the other 18 (51%, group 2) did not. Abnormal body surface maps were found in 100% of group 1 and 88% of group 2 patients (NS). In group 1, the provoked hypoperfusion was of greater extent (P=0.007) and severity (P=0.01) and the onset of map abnormalities was significantly earlier (P<0. 001) than in group 2; time to map abnormalities was also significantly shorter than time to ST segment depression (P=0.01). In the 35 patients with complete scintigraphic, body map and angiographic data, the severity of reversible perfusion defect proved to be the strongest correlate of ST segment depression upon logistic regression analysis. Thus, sestamibi SPET abnormalities after dipyridamole are almost always associated with electrical changes on body surface maps, suggesting myocardial ischaemia as their cause. The much less common 12-lead ECG changes are slower to appear and reflect a more severe hypoperfusion.

Body Surface Potential Mapping↗
PubMed1997

Ischemic burden in silent and painful myocardial ischemia: a quantitative exercise sestamibi tomographic study.

OBJECTIVES: We sought to determine whether the amount of myocardial ischemic burden differs in patients with painful or silent myocardial hypoperfusion during exercise testing. BACKGROUND: Whether a lack of symptoms during ischemia reflects an alteration in pain perception or less myocardium in jeopardy remains a controversial issue. METHODS: We studied 300 consecutive patients with a well established history of ischemic heart disease and reversible hypoperfusion on exercise sestamibi tomography. Rest and stress sestamibi defects were quantitatively assessed and indexes of exercise left ventricular dilation derived. RESULTS: Painful and silent reversible ischemia was observed in 97 (32%) and 203 (68%) patients, respectively. Patients with painful ischemia had lower values for work load, exercise time and peak rate-pressure product (p < 0.01) and more frequently showed significant ST segment depression during exercise than did patients with silent ischemia (69% vs. 40%, p < 0.001). On sestamibi tomography, patients with painful ischemia had more reversible hypoperfusion than did patients with silent ischemia (mean +/- SD 16 +/- 10% vs. 11 +/- 7%, p < 0.001), despite a comparable extent of stress hypoperfusion (22 +/- 12% vs. 22 +/- 13%); they also had a higher endocardial dilation index (1.32 +/- 0.32 vs. 1.10 +/- 0.26, p < 0.001). By multivariate logistic analysis, the most powerful correlate of painful ischemia was a history of effort angina; the extent of reversible perfusion defect was the sole independent scintigraphic correlate of painful ischemia. CONCLUSIONS: To our knowledge, this is the largest study comparing the degree of hypoperfusion and the presence of symptoms during exercise stress testing in a consecutive cohort of patients with ischemic heart disease and reversible hypoperfusion. The results suggest that the ischemic burden is greater in painful than in silent ischemia.

Adult↗
PubMed1997

Detection of hepatitis C virus RNA in CD19 peripheral blood mononuclear cells of chronically infected patients.

The presence of HCV RNA in peripheral blood mononuclear cells (PBMC) has been reported. To identify the cell populations carrying HCV RNA, the presence and amount of HCV RNA was investigated by limiting dilution nested reverse transcriptase-polymerase chain reaction (PCR) in PBMC subpopulations fractionated by automated cell sorting. Fifteen chronically HCV-infected patients were included in the study, 4 of whom also had mixed cryoglobulinemia. HCV RNA was present in the CD19 cells of all 15 patients, but only 5 (35.7%) of 14 and 5 (41.6%) of 12 showed HCV RNA in CD3 and CD14 cells, respectively (P < .001 by Fisher's test for each comparison). The median titer of HCV RNA was 1 PCR unit/380 CD19 cells, compared with median of 1 PCR unit/6600 PBMC as a whole. Titration was difficult in the CD3 and CD14 cells because of the frequent negativity of the first diluted sample. This study suggests that HCV RNA is selectively concentrated in B cells.

Adult↗
PubMed1997

Homozygous delta 32 deletion of the CCR-5 chemokine receptor gene in an HIV-1-infected patient.

BACKGROUND: Recent research has found that entry of non-syncytium-inducing (NSI), monocyte-macrophage-tropic HIV-1 isolates requires binding to both CD4 and CCR5 receptors, and that delta 32/delta 32 homozygous individuals are protected against infection. OBJECTIVE: To analyse the polymorphism of CCR-5 gene in HIV-1-infected and uninfected subjects. DESIGN AND METHODS: CCR-5 sequences were amplified by polymerase chain reaction (PCR) from DNA of peripheral blood mononuclear cells. Samples from 152 HIV-1-infected subjects and 122 uninfected controls were tested for the detection of the 32 base-pair deletion. HIV-1 phenotype was determined by viral isolation and MT-2 evaluation. RESULTS: The wild-type/delta 32 heterozygous and delta 32/delta 32 homozygous conditions were represented in 10.7 and 0.8% of healthy controls and in 9.8 and 0.7% of HIV-1-infected subjects, respectively. Of note, the delta 32/delta 32 deletion of the CCR-5 gene was detected by PCR and sequencing confirmed in a patient with progressive infection harbouring a clade B virus with SI phenotype. CONCLUSIONS: delta 32/delta 32 homozygosity for the CCR-5 gene does not confer absolute protection against HIV-1 infection, suggesting that either macrophage-tropic viral strains could use coreceptors other than CCR-5 or infect independently of the presence of a functional CCR-5 coreceptor. Alternatively, primary infection sustained by T-cell-tropic isolates, although exceptional, may occur.

Adult↗
PubMed1997

Evaluation of pulmonary ventilation and diaphragmatic movement in idiopathic scoliosis using radioaerosol ventilation scintigraphy.

Regional distribution of lung ventilation and diaphragmatic movement were evaluated using a non-invasive scintigraphic method in patients with idiopathic scoliosis. Twenty-four non-smoking patients aged 20 +/- 9 years (mean +/- S.D.), all with a right convex dorsal curve (mean Cobb's angle of 65.1 +/- 26.4 degrees), underwent lung ventilation scintigraphy after inhalation of 99Tcm-labelled human albumin microspheres. The distribution of the inhaled aerosol was assessed and scored based on four scintigraphic patterns, ranging from homogeneous distribution (score = 1) to diffuse severe hypoventilation (score = 4). Diaphragmatic movement, evaluated in 11 of the 24 patients, was assessed using an index (DM-Index) computed for each hemi-diaphragm by the normalization and subtraction of two digital scans obtained during maximal inspiration and expiration respectively. The left lung, situated on the concave side of the scoliotic curve, showed a more uneven distribution of ventilation (scintigraphic score: 2.62 +/- 1.17 vs 1.50 +/- 1.02, P < 0.01) and a reduced hemi-diaphragm movement (DM-Index: 29.2 +/- 4.0 vs 35.9 +/- 2.9, P < 0.001). A significant inverse correlation was found between Cobb's angle and both the right and left DM-Index (r = -0.82 and -0.66 respectively). In a stepwise multiple-regression analysis, the scintigraphic score correlated significantly with the functional index of distribution of inspired gas (IDI) derived from the multiple-breath nitrogen washout curve (P = 0.02). We conclude that lung ventilation scintigraphy provides information on the regional distribution of ventilation and on diaphragmatic movement in idiopathic scoliosis. The pulmonary function derangements in scoliotic patients were mainly localized in the lung on the concave side of the scoliotic curve and were related to the severity of the spinal curvature.

Adult↗
PubMed1997

Plasma viremia and virus phenotype are correlates of disease progression in vertically human immunodeficiency virus type 1-infected children.

OBJECTIVE: To analyze the relationships among HIV-1 plasma viremia, phenotype and CD4 T cell counts in vertically infected children. METHODS: Plasma viremia was quantified in 37 vertically infected children at different stages of the disease by a standardized molecular assay. Virus isolation and non-syncytia-inducing or syncytia-inducing (SI) HIV-1 phenotype evaluation were performed in parallel. RESULTS: HIV-1 RNA genomes were found to be significantly different in CDC clinical classes N, A, B and C (P = 0.0135) and in immunologic classes 1, 2 and 3 (P = 0.0110). None of the children in Class N or A harbored HIV-1 isolates with SI phenotype, whereas SI primary isolates were detected in 2 of 7 (29%) and 7 of 10 (70%) Class B and C children, respectively. Similarly SI variants were present in only 9 of 13 children in immunologic Class 3 (70%). When stratified according to the increasing severity of virologic status, the children showed a significant difference (P = 0.0458) in viral burden. CONCLUSIONS: Clinical symptoms, the most dramatic being reduction in the number of CD4 lymphocytes, and the highest plasma viremia levels were observed in the children in whom fast replicating, highly cytopathic SI variants were isolated. These data extend the virologic characterization of vertically HIV-1 infected children and suggest that both the plasma viremia levels and phenotype of primary isolates are viral correlates of disease progression in vertically infected children.

Anti-HIV Agents↗
PubMed1997

Long-term resistance to HIV infection in vertical HIV infection: cytokine production, HIV isolation, and HIV phenotype define long-term resistant hosts.

We analyzed immunologic (CD4 and CD8 slopes; interferon-gamma, interleukin-2, interleukin-10, and chemokines production; concentration of IgE; beta 2-microglobulin) and virologic (p24; HIV isolability and phenotype; plasma viremia) parameters in HIV vertically infected children > or = 8 years of age without disease progression or mild symptoms and an absolute CD4+ count > or = 500/microliter with CD4+ percentage > or = 25%. The results were compared to those of two control groups: (1) slow progressors, children > or = 8 years of age with moderate symptomatology and/or moderate CD4 depletion, and (2) progressors, children > or = 8 years of age with severe clinical disease and/or severe CD4 depletion. Pediatric long-term resistant hosts were characterized by higher production of interleukin-2 and interferon-gamma and lower production of interleukin-10, normal concentration of IgE, HIV isolates with a non-syncytium-inducing phenotype, and lower plasma viremia. This condition was not associated with the concentration of beta 2-microglobulin, p24, and chemokines, or with HIV isolability. The IL-10/IL-2 ratio best correlated with both CD4 counts and disease progression. Thus, vertically infected children showing resistance to disease progression are immunologically and virologically distinct from those in whom progressive HIV infection is observed.

Adolescent↗
PubMed1997

Loss of antiviral effect owing to zidovudine and lamivudine double resistance in HIV-1-infected patients in an ongoing open-label trial.

In order to compare the resistance pattern to zidovudine plus lamivudine in zidovudine-experienced patients, we studied three HIV-1-infected patients enrolled in NUCB3004, an open-label trial. Over a 24-week follow-up, the patients were studied for drug sensitivity, reverse transcriptase genotype, viral load (HIV-1 RNA level) and viral phenotype (syncytium inducing (SI) or non-syncytium inducing). Virus isolates derived from peripheral blood mononuclear cells (PBMCs) were tested for changes in drug susceptibility. Proviral DNA in the patients' PBMCs and RNA from plasma and culture supernatant were subjected to amplification and sequencing. All three HIV-1 strains showed a decreased susceptibility to either zidovudine or lamivudine after 24 weeks of therapy. The pattern of DNA genotypic resistance to lamivudine in patient A showed a mutation at codon 184 of the reverse transcriptase-encoding gene (methionine to valine). No HIV-1 strains with lamivudine-related mutations in proviral DNA were found among the isolates obtained from patients B and C. In these two patients, the mutation at codon 184 of the reverse transcriptase-encoding gene appeared in RNA, both in plasma and in culture supernatant. Viral phenotyping revealed the maintenance of the SI phenotype at week 24. Two out of the three patients experienced a reduction in HIV-1 RNA levels after 24 weeks of therapy, and in two out of three there was a rebound in viral load at week 28 together with the onset of the codon 184 mutation in RNA. The degree of phenotypic resistance to both zidovudine and lamivudine correlated with the amino acid changes in RNA and the rapid increase in viral load.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Different anticoagulant and immunological properties of anti-prothrombin antibodies in patients with antiphospholipid antibodies.

Lupus anticoagulant (LA) antibodies are acquired inhibitors of coagulation belonging-together with anticardiolipid (aCL) antibodies-to the family of antiphospholipid antibodies. Since LA antibodies affect coagulation reactions via recognition of the complex of lipid-bound prothrombin, they may be better named anti-prothrombin antibodies. We studied their immunological properties in the plasma of 59 patients with antiphospholipid antibodies by means of specific ELISA systems that allowed the characterization of the interaction of these antibodies with human prothrombin and anionic phospholipids. The mode of presentation of prothrombin was found to greatly influence the reactivity of anti-prothrombin antibodies. In fact, when plain polystyrene plates were used to immobilize prothrombin, virtually no binding was observed. Conversely, when prothrombin was coated on high-activated PVC ELISA plates, 34 samples (58%) contained antibodies that recognize human prothrombin in solid phase. In particular, IgG antibodies were found in 21 plasmas and IgM in 22; both IgG and IgM isotypes were present in 9 of these cases. A higher prevalence was observed in the ELISA for the detection of the antibodies directed at the calcium-mediated complex of phosphatidylserine (PS)-bound prothrombin: 53 samples (90%), preadsorbed with cardiolipin liposomes to remove aCL antibodies, showed the presence of IgG and/or IgM anti-prothrombin antibodies. When the results were analyzed according to the immunoglobulin isotypes, 44 (75%) and 39 (66%) samples were found to contain IgG and IgM anti-prothrombin antibodies, respectively. Both IgG and IgM were present in the plasma of 30 patients. Only half of these samples reacted also with PVC-bound prothrombin. Apparently, the higher rate of positivity of the ELISA for the detection of antibodies to the complex of PS-bound prothrombin was not due to differences in the amount of antigen available in the 2 systems, as judged by binding experiments performed with a rabbit polyclonal anti-human prothrombin antiserum. Finally, the anticoagulant properties of 14 total IgG preparations (12 of them contained anti-prothrombin antibodies positive in both ELISA systems, whereas the other 2 cases reacted either with PVC-bound prothrombin only or with PS-bound prothrombin only) were evaluated by diluted Russell's Viper Venom Time and by diluted activated Partial Thromboplastin Time. To rule out the beta 2-glycoprotein I (beta 2-GPI)-dependent anticoagulant effect of the aCL antibodies contained in the preparations, the coagulation tests were performed in beta 2-GPI deficient plasma. Six preparations failed to show anticoagulant activity in both assay systems, suggesting that 2 types of IgG anti-prothrombin antibodies exist, that differ with respect to their anticoagulant properties. These findings suggest that anti-prothrombin antibodies resemble aCL antibodies with respect to the behaviour in "in vitro" coagulation reactions and underline the wide heterogeneity of antiphospholipid antibodies.

Adult↗
PubMed1997

Rest-redistribution thallium-201 and rest technetium-99m-sestamibi SPECT in patients with stable coronary artery disease and ventricular dysfunction.

UNLABELLED: Resting sestamibi uptake was compared with 201Tl rest-redistribution uptake in 48 patients with ischemic heart disease and regional ventricular asynergies. METHODS: In 48 patients, rest/4-hr redistribution 201Tl and resting sestamibi tomography were closely performed on separate days. Segmental tracer uptake was quantified. Wall motion in corresponding segments was also assessed by two-dimensional echocardiography in 17 patients. RESULTS: Quantitative analysis indicates that the uptake of the two tracers was comparable in normal segments as well as in segments with fixed 201Tl defects. In contrast, in segments with reversible 201Tl defects, sestamibi uptake was significantly lower than redistribution 201Tl uptake. CONCLUSION: In patients with chronic ischemic heart disease and regional asynergies, quantified sestamibi activity parallels 201Tl redistribution activity in normal segments and in those with fixed 201Tl defects. In segments showing reversible 201Tl defects, whether or not dysfunctioning, sestamibi uptake is significantly lower than 201Tl redistribution.

Aged↗