Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 14 de 14
Filter
1.
J Acquir Immune Defic Syndr ; 24(3): 232-40, 2000 Jul 01.
Article in English | MEDLINE | ID: mdl-10969347

ABSTRACT

We evaluated the prevalence of both Q151M and 6-bp insert at position 69 of RT region responsible for multiple dideoxynucleoside analogue-resistant (MddNR) HIV-1 variants in 177 patients who failed to respond to combination therapy. Patients had received protease inhibitors (PI) and/or nonnucleoside reverse transcriptase inhibitors (NNRTIs) after a long-term experience with nucleoside reverse transcriptase inhibitors (NRTIs) (including zidovudine monotherapy). Two of 177 patients (1.1%) showed the specific complex of Q151M mutation, while 4 (2.3%) had the 69 6-bp insert. Mutations that belong to the 151 set in the absence of the pivotal Q151M substitution were detected in as many as 3.9% of the patients. One patient exhibited a 69S [VG] insert that has not been previously phenotypically characterized. This HIV-1 isolate had high levels of resistance to all NRTIs except stavudine. MddNR is an emerging problem after sequential therapy with this class of compounds among HIV-1-infected patients. Either didanosine (ddI) or zidovudine (ZDV) monotherapy allowed the emergence of MddNR variants containing Q151M complex. Monotherapy with ZDV and ddI or subsequent treatments with various NRTI combinations were the common background in the patients with the 69 insert. The overall prevalence of MddNR (3.4%) in Italy is comparable with that observed in several other European countries (3.4%-6.5%). These data suggest that patients failed by NRTI regimens should be analyzed for the presence of both patterns of MddNR.


Subject(s)
Dideoxynucleosides/therapeutic use , HIV Infections/drug therapy , HIV-1/drug effects , Reverse Transcriptase Inhibitors/therapeutic use , Acquired Immunodeficiency Syndrome/drug therapy , Adult , Aged , Amino Acid Sequence , Cohort Studies , Consensus Sequence , Didanosine/therapeutic use , Drug Resistance, Microbial/genetics , Drug Resistance, Multiple/genetics , Drug Therapy, Combination , Female , HIV Infections/immunology , HIV Infections/virology , HIV Reverse Transcriptase/genetics , HIV-1/enzymology , HIV-1/genetics , Humans , Italy/epidemiology , Male , Middle Aged , Molecular Sequence Data , Multicenter Studies as Topic , Mutagenesis, Insertional , Mutation , Prevalence , Protease Inhibitors/therapeutic use , Zidovudine/therapeutic use
2.
Clin Chim Acta ; 298(1-2): 181-6, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10876014

ABSTRACT

Serum transferrin saturation (TS) values were calculated on the basis of serum iron and transferrin (protein) measurements in a total of 2425 serum samples from six groups of subjects: individuals applying for selection as blood donors (M and F, median age 34 and 32 years); patients referring to the hospital laboratory for routine testing (M and F, median age 45 and 48 years); and elderly subjects living in a specialized institute (M and F, median age 76 and 82 years). In the first four groups the frequency of TS values <15% and >62% respectively, was substantially as expected, considering the average health conditions and sex. These results indirectly support the reliability of the measurement procedure. In the elderly group, however, the frequency of TS values >62% was zero. Mean TS values in the elderly group (males and females) were significantly lower (P<0. 0001) than in the blood donors group and in the hospital patients one. This observation suggests a shortened survival in the presence of (unrecognized) iron overload, pointing out at the usefulness of iron overload screening using simple biochemical tests.


Subject(s)
Aging/blood , Transferrin/metabolism , Adult , Aged , Aged, 80 and over , Female , Humans , Iron/blood , Iron Deficiencies , Iron Overload/blood , Male , Middle Aged , Molecular Weight , Reference Values , Transferrin/analysis
3.
Antivir Ther ; 5(1): 7-14, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10846586

ABSTRACT

We retrospectively studied 38 Italian recently HIV-1-infected subjects who seroconverted from 1994 to 1997 to investigate: (i) the prevalence of nucleoside reverse transcriptase inhibitors (NRTI)-related mutations at primary infection; (ii) the proportion of naturally occurring mutations in reverse transcriptase (RT) and protease regions of patients naive for non-nucleoside RT inhibitors (NNRTIs) and protease inhibitors (PIs); (iii) the drug-susceptibility to NRTIs and PIs in subjects with NRTI- and/or PI-related mutations; and (iv) the outcome of seroconverters treated with various NRTIs or NRTI/PI regimens. Baseline HIV-1 plasma viraemia and absolute CD4 count at baseline could not be used to distinguish patients with NRTI- and/or PI-related pre-existing mutations from those with wild-type virus (P = 0.693 and P = 0.542, respectively). The frequency of zidovudine-related mutations was 21% in the study period. The response to treatment was not significantly different in subjects with or without genotypic zidovudine-related mutations at primary infection (P = 0.744 for HIV-1 RNA and P = 0.102 for CD4 cells). Some natural variation (2.6%) was present within regions 98-108 and 179-190 of RT involved in NNRTI resistance. The high natural polymorphism in the protease region present in our patients was similar to that reported by others. In our study some PI-associated substitutions, thought to be compensatory in protease enzymatic function, could confer intermediate to high PI-resistance. As discrepancies between genotypic and phenotypic results may exist in recent seroconverters, our data suggest that the role of transmitted NRTI- and PI-resistant variants remain to be fully elucidated in vivo.


Subject(s)
Anti-HIV Agents/pharmacology , HIV Infections/virology , HIV-1/drug effects , Mutation , Reverse Transcriptase Inhibitors/pharmacology , Anti-HIV Agents/therapeutic use , Drug Resistance, Microbial/genetics , Drug Therapy, Combination , Gene Products, pol/genetics , Genotype , HIV Infections/drug therapy , HIV Infections/immunology , HIV Protease/genetics , HIV Reverse Transcriptase/genetics , HIV-1/genetics , Humans , Indinavir/pharmacology , Indinavir/therapeutic use , Phenotype , RNA, Viral/blood , Retrospective Studies , Reverse Transcriptase Inhibitors/therapeutic use , Ritonavir/pharmacology , Ritonavir/therapeutic use , Treatment Outcome , Zidovudine/pharmacology , Zidovudine/therapeutic use
4.
J Biol Regul Homeost Agents ; 14(1): 51-7, 2000.
Article in English | MEDLINE | ID: mdl-10763895

ABSTRACT

Twenty-nine HIV-1 recently infected subjects were retrospectively studied to investigate both the prevalence of nucleoside reverse transcriptase inhibitors (NRTI)-related mutations at primary infection and the proportion of naturally occurring mutations in protease inhibitor (PI)-naive patients. Neither HIV-1 plasma viremia nor CD4 absolute count at baseline could distinguish patients with NRTI pre-existing mutations from those with wild-type virus. An increasing proportion of ZDV-related mutations was observed over time with an overall frequency of 20.7% in the study period. Only 1 out of 6 patients (16.7%) with ZDV-related mutations showed a phenotypically ZDV resistant isolate. A striking proportion of polymorphic changes was present in the protease region of pol gene in newly infected individuals. As many as 80% of seroconverters presented at least one naturally occurring substitution. Some PI-associated substitutions, thought to be compensatory in protease enzymatic function, could confer intermediate to high PI-resistance. Their role following PI administration remains to be elucidated. Our data suggest that the choice of drugs should be oriented by both genotypic and phenotypic evaluations to tailor individual regimens in seroconverters.


Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , HIV-1/drug effects , Acquired Immunodeficiency Syndrome/virology , Drug Resistance , Genotype , HIV Protease/genetics , Humans , Mutation , Phenotype , RNA, Viral/blood , Retrospective Studies , Zidovudine/pharmacology
5.
J Infect Dis ; 180(2): 285-9, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10395841

ABSTRACT

Stromal-derived factor (SDF)-1, the natural ligand for CXCR4, is present in a common polymorphic variant defined by a G-->A transition in the 3' untranslated region of the gene. In persons infected with human immunodeficiency virus type 1 (HIV-1), the homozygous genotype (SDF1-3'A/3'A) has been postulated to interfere with the appearance of T-tropic syncytium-inducing strains. The polymorphism of SDF1 was correlated with HIV-1 phenotype, plasma viremia, and unspliced and multiply spliced specific transcripts in 158 virologically characterized HIV-1-infected patients (39 recent seroconverters, 75 typical progressors, and 44 AIDS patients) and in 42 HIV-1-infected long-term nonprogressors (LTNPs). Analysis of SDF1 allele distribution revealed that SDF1-3'A/3'A status is associated with low CD4 cell count (P=.0449) but not with a specific HIV-1 phenotype. In LTNPs, SDF1-+/+ condition defined a subset of persons with lower HIV-1 replication than in heterozygous subjects. The low viral activity in SDF1-+/+ LTNPs suggests that other factors play a major role in vivo in determining the course of HIV-1 infection.


Subject(s)
Chemokines, CXC/genetics , HIV Infections/virology , HIV Long-Term Survivors , HIV-1/isolation & purification , Polymorphism, Genetic , Adult , Aged , Chemokine CXCL12 , Female , Giant Cells/immunology , Giant Cells/virology , HIV Infections/genetics , HIV Infections/immunology , HIV-1/genetics , HIV-1/physiology , Humans , Male , Middle Aged , Phenotype , Polymerase Chain Reaction/methods , Polymorphism, Restriction Fragment Length , RNA, Viral/blood , Reverse Transcriptase Polymerase Chain Reaction , Virus Replication
6.
Clin Immunol Immunopathol ; 85(3): 320-3, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9400632

ABSTRACT

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.


Subject(s)
Acquired Immunodeficiency Syndrome/immunology , CD4 Lymphocyte Count , HIV Antibodies/blood , HIV-1/immunology , Acquired Immunodeficiency Syndrome/blood , Adult , Disease Progression , Female , HIV Antibodies/immunology , HIV Envelope Protein gp120/blood , HIV Envelope Protein gp120/immunology , HIV Seropositivity/immunology , Humans , Male , Sialoglycoproteins/blood , Sialoglycoproteins/immunology
7.
AIDS ; 11(10): F67-71, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9256936

ABSTRACT

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.


Subject(s)
HIV Seropositivity/genetics , HIV-1/pathogenicity , Mutation , Polymorphism, Genetic , Receptors, Cytokine/genetics , Receptors, HIV/genetics , Adult , Cloning, Molecular , Cohort Studies , HIV Envelope Protein gp120/genetics , HIV Seropositivity/epidemiology , HIV-1/classification , Heterozygote , Humans , Immunity, Innate/genetics , Italy/epidemiology , Male , Polymerase Chain Reaction , Receptors, CCR5 , Risk Factors , Sequence Analysis, DNA , Sequence Deletion , Viremia/diagnosis , White People/genetics
8.
J Pain Symptom Manage ; 12(1): 18-22, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8718912

ABSTRACT

Anemia is often associated with neoplastic disorders. Blood transfusions are used to alleviate the discomfort of anemic cancer patients. Of 246 terminally ill cancer patients admitted to our palliative care unit from October 1991 to December 1993 (128 women and 118 men), 31 patients (12.6%) (17 men and 14 women; age, 69.5 +/- 12 years) received on average 2.8 units of packed red blood cells (PRBCs) (range, 2-7 units/patient) in 35 separate admissions. PRBCs were transfused in the presence of low hemoglobin (Hb) levels ( < or = 8 g/dL) and/or severe fatigue or dyspnea. Pre-transfusion performance status, cognitive function, dyspnea, and fatigue at rest (evaluated by a four-point scale), complete blood count, serum albumin, and C-reactive protein were determined. The day after transfusion, subjective well-being was recorded as "yes/no" improvement in comparison with the pre-transfusion day. Improved subjective well-being after blood transfusion was reported in 51.4%, without significant relationship to pre-transfusion Hb levels or performance status. The influence of blood transfusion on subjective well-being was not related to the severity of dyspnea or fatigue. Twenty-one patients (60%), including seven with subjective improvement, died during the same hospitalization, a median of 49 days after transfusion. Pre-transfusion Hb level did not differ significantly in patients who benefited and did not benefit from transfusion, whereas time before death was significantly (P < 0.001) shorter in patients who did not benefit. In the discharged patients (40%), the median interval between transfusion and discharge was 13 days and the frequency of subjective improvement in well-being was 78.6%. Our data suggest that two main areas should be investigated, namely the relation between low Hb levels and symptoms and signs in terminally ill cancer patients, and the correct timing for effective blood transfusion. A combination of criteria is needed for effective transfusion; they must include not only Hb levels but also type and severity of anemic symptoms and signs. Furthermore, the identification of reliable prognostic indicators for survival would be useful.


Subject(s)
Anemia/therapy , Erythrocyte Transfusion , Neoplasms/complications , Aged , Erythrocyte Count , Female , Humans , Male , Palliative Care , Retrospective Studies , Terminal Care
9.
Blood ; 88(2): 574-9, 1996 Jul 15.
Article in English | MEDLINE | ID: mdl-8695805

ABSTRACT

Human immunodeficiency virus (HIV) isolability, rate of viral replication, HIV phenotype, type 1 and type 2 cytokine production, and CD4 counts were cross sectionally analyzed in 63 HIV seropositive (HIV+) individuals to establish possible correlations between virologic and immunologic markers of protection and progression. We observed that these markers are tightly correlated. Thus, lack or low prevalence of HIV isolability and the presence of nonsyncitium inducing strains are associated with the strongest type 1 cytokine production, the weakest type 2 cytokine production, and highest CD4 counts. Conversely, the isolation of highly replicating, syncitium-inducing HIV strains is associated with the weakest type 1 cytokine production, the strongest type 2 cytokine production, and lowest CD4 counts. Additionally, it was determined that the interleukin (IL)-10/IL-2 ratio best discriminates among different virologic scenarios. These data suggest that the virologic and immunologic correlates of disease protection and progression might be associated variables that define two different subsets of HIV+ individuals and lend support to a viro-immunologic hypothesis of HIV infection.


Subject(s)
CD4-Positive T-Lymphocytes/metabolism , HIV Infections/epidemiology , HIV-1/isolation & purification , Interleukin-10/metabolism , Interleukin-2/metabolism , Biomarkers , CD4 Lymphocyte Count , Comorbidity , Cytopathogenic Effect, Viral , Disease Progression , Female , HIV Infections/blood , HIV Infections/immunology , HIV Infections/virology , HIV-1/genetics , HIV-1/physiology , Humans , Italy/epidemiology , Male , Phenotype , Prospective Studies , Risk Factors , Sexual Behavior , Substance Abuse, Intravenous/epidemiology , Virus Replication
10.
Antimicrob Agents Chemother ; 39(12): 2819-21, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8593030

ABSTRACT

More than 250 Providencia strains isolated from the urine of institutionalized elderly patients were tested against cefaclor, cefuroxime, cefetamet, cefpodoxime, ciprofloxacin, and amoxicillin-clavulanic acid. Our results confirm the strong activities of expanded-spectrum oral cephalosporins against Providencia isolates, f1p4ell as the marked differences in susceptibilities among accurately identified Providencia species.


Subject(s)
Anti-Bacterial Agents/pharmacology , Enterobacteriaceae Infections/microbiology , Providencia/drug effects , Urinary Tract Infections/microbiology , Administration, Oral , Aged , Anti-Bacterial Agents/administration & dosage , Humans , Institutionalization , Microbial Sensitivity Tests
11.
J Chemother ; 3 Suppl 1: 62-5, 1991 Jan.
Article in English | MEDLINE | ID: mdl-12041788

ABSTRACT

997 strains isolated from clinical specimens arrived at the "Pio Albergo Trivulzio" microbiology laboratory were tested using disks of cefpodoxime, amoxicillin + clavulanic acid, cefaclor, cefuroxime, ofloxacin, cotrimoxazole, ceftriaxone and cefalexin. Gram-positive strains were tested also with erythromycin, while gram-negative bacteria were tested against aztreonam. Cefpodoxime overall activity was well above the effectiveness of the other oral cephalosporins and on the same order as ceftriaxone and ofloxacin. Cefpodoxime proved to be also more active than the combination amoxicillin-clavulanic acid.


Subject(s)
Anti-Bacterial Agents/pharmacology , Ceftizoxime/analogs & derivatives , Ceftizoxime/pharmacology , Aged , Bacterial Infections/drug therapy , Diffusion Chambers, Culture , Humans , Microbial Sensitivity Tests , Cefpodoxime Proxetil
12.
Boll Ist Sieroter Milan ; 68(3): 277-83, 1989.
Article in Italian | MEDLINE | ID: mdl-2491437

ABSTRACT

A peptide (called A-15) composed of 15 amino acids of the gp41 (from position 599 to position 613 of the sequence encoded by the env gene) of HIV-1 has been used as an antigen to search for antibodies in 347 sera of at-risk for HIV-1 infection subjects. The purpose was of comparing the prevalence of these antibodies with that of HIV-1 total EIA antibodies and HIV-1 immunoblotting antibodies. Assuming immunoblotting test as reference test for detecting a HIV-1 infection, the antibodies against peptide A-15 show the same sensitivity and specificity when compared with other HIV-1 total EIA antibodies tests.


Subject(s)
HIV Antibodies/blood , HIV Envelope Protein gp41/immunology , HIV Infections/diagnosis , HIV-1/immunology , Amino Acid Sequence , Antibody Specificity/immunology , Female , HIV Infections/immunology , Humans , Immunoblotting , Immunoenzyme Techniques , Male , Molecular Sequence Data
13.
Int J Tissue React ; 10(6): 373-9, 1988.
Article in English | MEDLINE | ID: mdl-2475452

ABSTRACT

We have examined the effects of oxygen free radicals, generated by xenobiotics administration, ischaemia-reperfusion or sepsis, on the healing of skin or intestinal wounds in rats. We found that 5 days after operation there was a significant decrease in the wound breaking strength in rats treated with phenazine methosulfate, zymosan, ischaemia-reperfusion or retroperitoneal infection. These changes were specifically prevented by administration of superoxide-dismutase (SOD), aprotinin and (in some models) allopurinol. On the contrary, none of these measures was effective when a local trauma caused the decrease in breaking strength. Our results suggest that oxygen free radicals mediate the inhibition of wound healing following ischaemia-reperfusion and sepsis.


Subject(s)
Aprotinin/therapeutic use , Oxygen/metabolism , Superoxide Dismutase/therapeutic use , Wound Healing/drug effects , Allopurinol/therapeutic use , Animals , Female , Free Radicals , Methylphenazonium Methosulfate/pharmacology , Rats , Rats, Inbred Strains , Xenobiotics/pharmacology , Zymosan/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL
...