HIV-1 seroconversion in pregnancy without materno-fetal transmission of the virus.
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Biomedical subjects
Publications and source records attributed to M Pecorari.
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The antibody content to HIV-1 p24 Ag expressed as relative binding capacity to the target antigen (p24 RBC) was retrospectively quantified in serum samples from 20 HIV-1-uninfected infants born to HIV-1 seropositive mothers. p24 RBC values quantified at birth were included either in a low (0-20%) or high (80-100%) range of values, classified as group A (11 infants) and group B (9 infants), respectively. The course of maternal antibodies to HIV-1 antigens p17, p24, p31, gp41, p51, p66, gp120, and gp160 was studied in each group. A substantial difference in the amount and subsequently in the decline of maternal antibodies to gag proteins p17, p24, and p55 and to pol proteins p51 and p66 was observed in the two infant groups in contrast with a similar content and decline of the remaining antibodies. In 7 HIV-1-infected infants of whom 4 resembled infant group A and 3 infant group B for p24 RBC values, a relationship appeared between p24 antibody decline and p24 antigenemia detection.
AIMS: To evaluate the presence of cytomegalovirus (CMV) DNA in the cerebrospinal fluid of patients with AIDS and suspected viral encephalitis using an in situ hybridisation assay with digoxigenin labelled CMV DNA probes. METHODS: The presence of CMV DNA was evaluated in cerebrospinal fluid cells of 10 patients with AIDS using in situ hybridisation. The positivity of CMV DNA was confirmed by the presence of CMV induced antigens in the same specimens. The presence of CMV DNA and CMV induced antigens was also analysed in peripheral blood leucocytes. The time required to perform the in situ hybridisation assay was about eight hours. RESULTS: The in situ hybridisation assay was sensitive, specific, and provided good resolution. Six patients proved positive for the presence of CMV DNA in CSF cells and all six also proved positive for CMV DNA in blood leucocytes. Of the six CMV positive patients, five were treated with specific antiviral drugs: of these, one died during the treatment while four clinically recovered after one month of treatment. CONCLUSIONS: The in situ hybridisation assay using digoxigenin labelled CMV DNA probes can be used as a valuable diagnostic test for the detection of CMV DNA in the cerebrospinal fluid cells of patients with suspected CMV encephalitis and can therefore prompt adequate antiviral therapeutic intervention.
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We investigated the presence of the HIV-1 infection using the polymerase chain reaction (PCR) test in seronegative sexual partners of HIV-infected subjects and in children born to seropositive mothers. By using PCR assay, no HIV-1 DNA was detected in 32 female partners of HIV positive patients including three pregnant women who were also studied during pregnancy and after delivery. HIV-1 DNA was found in 12 out of 38 children born to seropositive mothers; five of them also had detectable serum HIV-1 p24 Ag levels. On the whole, our data stress the importance of using a very sensitive technique, i.e. PCR, for the early diagnosis of HIV-1 infection.
Sera from a sample of healthy Italian people were tested in an indirect immunofluorescence assay (IFA) for reactivity to a Human Herpesvirus-6 (HHV-6) strain called CV, isolated from a baby with exanthem subitum (Portolani et al., 1990). Seropositivity values of 83.78%, 92.68% and 63.64% were found in subjects aged 3 months-6 years, 6-18 years and over 18 years respectively. Sera from cordal blood, sera from subjects with evidence of active infection by Cytomegalovirus (CMV) or by Epstein-Barr virus (EBV), sera from seropositive adults to Human Immunodeficiency Virus type 1 (HIV) were also investigated for antibodies to the same HHV-6 strain. Values of antibody incidence and antibody content to HHV-6 in these groups of sera were generally higher than in the other groups. HHV-6 reinfections of both endogenous and exogenous origin and antibody cross-reactivity were considered among the reasons of this increase. HHV-6 seropositivity values in healthy Italian people and in people from different countries were also discussed in the light of the antigenic characteristics of the HHV-6 strains used and of the different test conditions.
Peripheral blood cultures from children showing symptoms of generic infectious disease have been examined for human herpesvirus-6 (HHV-6). Two HHV-6-related isolates have been obtained: one from a child for whom a clinical diagnosis of exanthema subitum has been made when a typical rash appeared, and one from a child in whom the infectious symptomatology has maintained the characters of nonspecific syndrome. All the syndrome diagnosed as exanthema subitum resulted as being associated with fresh infection by HHV-6-related virus.
Sulfate glycolithocholic acid (SGLC) has been shown to be highly cholestatic in the rat. This study was performed in order to gain understanding of the mechanisms of SGLC-induced cholestasis and the aim of the investigation was to explore the hypothesis that SGLC could cause a precipitation of calcium in bile. We studied the effects of intravenously administrated SGLC on bile flow, biliary lipids secretion and calcium excretion in the female bile fistula hamster. We also performed in-vitro studies with a Ca2(+)-selective electrode in order to measure the calcium binding capacity of SGLC. The results showed that after 1 h of infusion of 8 mumol/100 g body weight [14C]SGLC bile flow dropped to zero. During the infusion period a fine white sludge was visible in the test tube used for bile collection. TLC and HPLC analysis of both the supernatant and the precipitate showed that unchanged SGLC was excreted into bile. Up to 20% of biliary SGLC and more than 50% of the total Ca2+ present in bile was precipitated. The SGLC/Ca2+ molar ratio in the precipitate was 1.12 +/- 0.3 (mean +/- S.D. of four experiments). Light and electron microscopy of the liver did not show any specific abnormalities. The Ca2+ binding activity of SGLC in vitro, was highest among the bile acids tested at a concentration of 0.1 mM, when almost 100% of bile acids are in the monomeric (non-micellar) form. This suggests that among the bile acids, SGLC exerts the strongest binding activity on free calcium ions.(ABSTRACT TRUNCATED AT 250 WORDS)
Several serological techniques may be used for the detection of HIV infection, however, in the case of infants, there are no methods that are effective prior to the loss of maternal antibodies. Thus, in such cases, a completed series of serological and virological assay of HIV antibodies should be performed in follow-up studies. Twenty children living in Modena (Italy) were studied since 1985. Seven of these children were of ages ranging from 3 to 10 years. Only one of them was found to be seropositive for HIV. The remaining 13 children were studied from birth. Six had lost maternal antibodies to HIV at a median age of 15.1 months. Four showed decreasing levels of the anti-body by Western blotting. HIV antigen was detected in serum samples from 2 children. The data reported stress the need for longitudinal studies that could lead to reliable methods of diagnosing HIV infections in newborns.
A commercial enzyme immunoassay was utilized for the detection of the human immunodeficiency virus antigen (p24) in serum samples from persons at risk for AIDS. The test demonstrated sensitivity to 20 pg/ml of serum antigen. The results obtained showed 14.63% of the subjects (Ss) with persistent generalized lymphadenopathy or asymptomatic Ss, and 69.23% of the Ss with AIDS related complex (ARC) or AIDS to be positive for HIV-Ag. In addition, there were no false-positives in the control serum samples collected from seronegative individual. The close correlation observed between HIV-Ag presence and advanced stages of the disease, stresses the diagnostic importance of this viral marker and its usefulness in the follow-up of Ss with HIV infection.
This study reports the effect of short-term tauroursodeoxycholic acid (TUDCA) and of TUDCA with addition of taurine on the lipid composition of gallbladder bile, on cholesterol and bile acid synthesis and intestinal excretion, in the female hamsters. After either one or two weeks, the percentage of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) in bile of treated hamsters significantly increased. Both treatments (TUDCA alone or TUDCA + taurine) decreased the percentage of cholic acid without affecting 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase or cholesterol 7 alpha-hydroxylase activities. Sterol and bile acid content of the feces collected during the period of the study did not show any difference. Bile acid glycine to taurine conjugation ratio (G/T ratio) in TUDCA treated animals was significantly higher in respect to controls after only one week of treatment. On the contrary, bile acid G/T ratio significantly decreased in the group of animals supplemented with taurine, but only after two weeks of treatment.
There is evidence that increased availability of taurine enhances the proportion of taurine-conjugated bile acids in bile. To explore the possibility that taurine treatment could also influence hepatic cholesterol and bile acid metabolism, we fed female hamsters for 1 week and measured both the biliary lipid content and the microsomal level of the rate-limiting enzymes of cholesterol and bile acid synthesis. In these animals the cholesterol 7 alpha-hydroxylase activity was significantly greater in respect to controls (P less than 0.05). The total HMG-CoA reductase activity, as well as that of the active form, was similarly increased. The stimulation of 7 alpha-hydroxycholesterol synthesis was associated with an expansion of the bile acid pool size in taurine-fed animals. Taurine feeding was observed to induce an increase in bile flow as well as in the rate of excretion of bile acids, whereas the secretion rate of cholesterol in bile was decreased. As a consequence, the saturation index was significantly lower in taurine-fed animals (P less than 0.05). The possible mechanisms through which taurine exhibits the modification of the enzyme activities and of the biliary lipid composition are discussed.
This study was aimed to ascertain whether the more acidic isoforms of plasma apo A-I (A-I-1 and A-I-2) could originate in vitro from the main plasma isoform (A-I0). Apo A-I isoforms were separated by two-dimensional gel electrophoresis before and after a prolonged incubation of serum or EDTA-plasma at 37 degrees C. Incubated plasma there was a marked decrease of apo A-I0 and a concomitant linear increase of apo A-I-1 + and A-I-2. The relative content of the latter raised from 22 +/- 7% before the incubation to 60 +/- 7% after 48 h of incubation. This conversion of A-I0 was not inhibited by either pre-heating of plasma at 60 degrees C for 1 h or the addition of protease inhibitors, EDTA and p-chloromercuriphenylsulfonic acid. The conversion of apo A-I0 was not observed in isolated HDL, incubated either in the absence or in the presence of d less than 1.063 g/ml lipoproteins and lipoprotein deficient plasma, nor in plasma which had been dialyzed before being incubated at 37 degrees C. This suggests that plasma contains a low molecular weight factor capable of promoting the conversion of A-I0. The increase of the relative content of apo A-I-1 and apo A-I-2 in incubated plasma was not due to glucosylation or carbamylation of A-I0 as no radioactive glucose and urea were found to be bound to A-I. Since the conversion of apo A-I0 was prevented by the addition of an antioxidant (butylated hydroxytoluene, BHT) to the incubated plasma it is conceivable that some product of lipid peroxidation renders apo A-I0 more electronegative by reacting with some free amino groups of this peptide.
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We compared apo A-I isolated from the lipoproteins of the Golgi apparatus of rat liver with apo A-I found in plasma lipoproteins. Golgi apo A-I consists of 3 main isoforms with a molecular weight of approximately 28000 and isoelectric points (pI) of 5.97, 5.88 and 5.76, respectively. Plasma apo A-I consists of 4 major and 3 minor isoforms with a molecular weight of 27000. The pI of the major isoforms (numbered 4-7) is 5.88, 5.80, 5.70 and 5.60, respectively. In order to investigate which of the plasma isoforms derived directly from Golgi apo A-I, [35S]methionine was injected into the portal vein and Golgi and plasma apo A-I were isolated shortly thereafter. While all Golgi isoforms were labelled only 3 isoforms of plasma apo A-I (namely isoforms 5, 6 and 7) were found to be labelled. The major plasma isoform (isoform 4 which accounts for more than 60% of apo A-I mass of plasma HDL) was found to be unlabelled. However, when 35S plasma lipoproteins newly secreted by the liver were incubated in vitro in the presence of heparinized plasma, labelled isoform 4 appeared suggesting that heparinized plasma contained some factor capable of converting isoforms 5-7 into isoform 4. This plasma factor appears to be a protease as the in vitro formation of isoform 4 is prevented by protease inhibitors.
Pharmacological interactions between protease inhibitors and tacrolimus require careful monitoring to prevent toxicity in the posttransplantation period. A 42-year-old man with human immunodeficiency virus (HIV) infection and end-stage liver disease due to hepatitis C virus (HCV) received an orthotopic liver transplant. At the time of surgery the patient was on triple antiretroviral therapy (tenofovir, lamivudine, and lopinavir/ritonavir) with a stable CD4(+) count (>500 cells/mm(3)) and HIV-1 RNA (<50 copies/mL). Immunosuppression was maintained with tacrolimus (0.5 mg at a single dose once per week). One month after surgery HCV recurrence was documented. Pharmacokinetic evaluation of lopinavir/ritonavir showed a rapid increase in the area under the curve. Drug concentrations returned to normal levels, with reduction in liver enzymes. At the same time, tacrolimus dosages were reduced to a maintenance dose of 0.5 mg every 2 weeks. The patient, at 17 months postoperatively, is alive in good health with normal liver function and HCV RNA load levels. This is the first case in which a profound change in the pharmacokinetics of a protease inhibitor caused by a drug-drug interaction was observed during transient liver damage. Because this clinical event is particularly common in HIV-infected patients, our findings suggest that therapeutic drug monitoring should be performed to determine the impact of potential drug interactions in the early posttransplantation period, at the time of resumption of therapy or introduction of new anti-retroviral therapy and during HCV recurrence in order to optimize both tacrolimus and protease inhibitor treatment.
This report describes three cases of posttransplant lymphoproliferative disorder (PTLD) in multivisceral/small bowel transplant patients treated with rituximab (anti-CD20 monoclonal antibodies). In two cases (one of which was a B-cell lymphoma) a good response to therapy was achieved. A third case (with polymorphic PTLD with low CD20 expression) developed a refractory rejection and PTLD was still documented on graftectomy. Rituximab was well tolerated, and a reduction of Epstein-Barr virus (EBV) viral load was documented by quantitive competitive-EBV polymerase chain reaction. Efficacy of therapy needs to be assessed in controlled studies.
In our dialysis unit, we commonly position permanent catheters (the Tesio twin catheter) in femoral veins with 'high' exit sites, in the abdominal area. We prefer this method because of its intrinsic safety in patients immediately requiring hemodialysis (HD), because there is no need for ultrasound guidance and a low incidence of complications during and after positioning. In addition, we consider that this method is suitable for older patients without good native vessels for an arteriovenous fistula (AVF). Sixty-nine femoral catheters were positioned in 61 patients (mean age 70.8 yrs): 307 observational months/patients (mean duration 4.45 months) demonstrated the following results: a) no incidents during catheter positioning; b) four iliac-femoral thromboses (in three cases complete recanalization with heparin treatment); c) two catheters were removed due to an infection of the tunnel; d) no generalized, life-threatening sepsis. Therefore, we recommend this solution as a 'bridge-access' between the immediate need for HD and the successive best strategy for the treatment of end-stage renal disease (ESRD).