Frequent cervicovaginal shedding of HIV-1 in asymptomatic, non-severely immunodeficient women.
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Cervix Uteri↗
Biomedical subjects
M Di Stefano
Publications and source records attributed to M Di Stefano.
Densitometric study of developing femur.
The purpose of this work was to extend to long bones the study on the ossification of human fetal skeleton in relation to conceptual age by a quantitative methodological approach. Postero-anterior scans were performed on 29 dried fetal femora (from 11.5 weeks of conceptual age to term) by a Hologic QDR 1000 X-ray densitometer with Ultra-Hi-Resolution software. The results were expressed as bone mineral content (BMC, g) and bone mineral density (BMD, g/cm2). BMD was calculated on a rectangular area corresponding to the total length and minimum width of the shaft. This area was divided into five equal sections along its longitudinal axis in order to estimate the rate of ossification from a spatio-temporal point of view. Our data show that BMC has a high correlation with conceptual age during the whole prenatal life, increasing in the third trimester (r >/= 0. 96). During development, BMD is progressively less correlated with conceptual age (r = 0.95 in the first half of development, r = 0.68 in the second half), particularly according to a bidirectional gradient from the middle to the proximal and distal ends of the shaft. Our findings confirm the data obtained in our previous studies on the ossification of fetal human spines, and suggest an individual variability in bone density at term of development and particularly at the level of spongiosa, viz. in the areas mostly involved in architectural changes during the morphogenesis of the long bones.
Absorptiometry, Photon↗
Bone metabolism in type 2 diabetes mellitus.
Several conditions have been described to cause osteoporosis, including diabetes mellitus. While the relationship between type 1 diabetes and osteopenia is well documented in the literature, data on the presence of this complication in type 2 diabetes have not been well established. We studied a population composed of 66 post-menopausal women with type 2 diabetes and a control population. We examined bone mineral density with the dual-energy X-ray absorptiometry (DXA) technique at the lumbar and femoral levels and, in a subgroup of patients, we also measured the levels of markers of bone remodelling. We found significantly higher levels of bone mineral density at the femoral (but not lumbar) level in the diabetic subjects compared with the control population in all the examined subregions, except Ward's triangle. Moreover, we found higher levels of some markers of bone resorption (urinary calcium and hydroxyproline, telopeptide) in the patients with diabetes, while urinary crosslinks were higher in the controls. On the basis of these results, we suggest that osteoporosis cannot be considered a complication of type 2 diabetes and that, from a metabolic point of view, bone resorption is greater in diabetic patients than in normal subjects, as suggested by the high levels of most of the markers of osteoclastic activity.
Absorptiometry, Photon↗
Bone mass and metabolism in dermatitis herpetiformis.
Dermatitis herpetiformis is a gluten-sensitive skin disease with intestinal lesions and malabsorption symptoms less severe than those found in celiac disease. While several studies have shown the occurrence of osteopenia in celiac disease, bone mass and metabolism have never before been evaluated in dermatitis herpetiformis. Therefore, in 16 untreated patients, 16 sex- and age-matched untreated celiac patients, and 16 sex- and age-matched healthy volunteers, lumbar and femoral bone mineral density were measured and bone and mineral metabolism and nutritional status were evaluated. All these parameters were significantly altered in the two groups of patients and although the degree of these alterations was milder in patients with dermatitis herpetiformis than in celiac patients, the presence of subtotal villous atrophy in patients with dermatitis herpetiformis was associated with the presence of more severe alterations. Bone mineral density was significantly correlated with nutritional status, and patients showing bone loss were characterized by a body mass index lower than 20. Alterations of bone mass and mineral metabolism complicate dermatitis herpetiformis when severe intestinal lesions coexist. A low nutritional status may be predictive of the presence of bone loss.
Absorptiometry, Photon↗
Reduced concentrations of HIV-RNA and TNF-alpha coexist in CSF of AIDS patients with progressive multifocal leukoencephalopathy.
OBJECTIVES: To confirm reduced human immunodeficiency virus type-1 (HIV-1) burden in the CSF of patients with progressive multifocal leukoencephalopathy (PML) and to verify whether this viral load coincides with the absence of inflammatory changes in the CSF. METHODS: Paired CSF and plasma samples from 17 patients with PML, 26 with non-PML cerebral opportunistic infections, nine with HIV-1 leukoencephalopathy (HIVE), and 12 neurologically asymptomatic AIDS patients were subjected to HIV-RNA titration. Tumour necrosis factor (TNF)-alpha was also measured and the CSF albumin: serum albumin ratio (Q(Alb)) was calculated. RESULTS: The CSF HIV-1 burden of patients with PML did not differ from that of neurologically asymptomatic patients (p=0.21), but was significantly lower than CSF burden of the remaining patients (non-PML opportunistic infections, p<0.001; HIVE, p<0.001). Q(Alb) was normal for all neurologically asymptomatic patients, for 86.6% patients with PML, and 62.5% patients with HIVE (p=0.09). Q(Alb) was altered in 91.6% patients with non-PML opportunistic infections. TNF-alpha in CSF was higher in patients with non-PML opportunistic infections (p<0.001) and those with HIVE (p<0.001) than in patients with PML who consistently had TNF-alpha concentrations<10 pg/ml. CONCLUSIONS: These results, while indicating a reduced HIV replication in CSF of patients with PML which might serve as a disease marker, emphasise the increased CSF HIV-RNA concentration in patients with HIVE and patients with non-PML opportunistic infections. Low concentrations of HIV-RNA in CSF coincide with reduced TNF-alpha concentrations, possibly due to particular features of PML compared with other opportunistic infections as it develops without detectable inflammatory changes in the CSF.
Acquired Immunodeficiency Syndrome↗
Phenotypic patterns of HIV-1 clonal populations during highly active antiretroviral therapy (HAART).
Several studies have demonstrated that during HIV-1 infection many different viral clones may co-exist in the same individual. These clones may differ regarding their biological phenotype and may influence both the natural history of infection and the clinical response to antiretroviral therapy. The aim of the present study was to investigate the influences of combination therapies including protease inhibitors (HAART) on the phenotypical pattern of HIV-1 biological clones in peripheral blood mononuclear cells. Viral isolation and biological characterisation of bulk isolates and clonal viral isolates were performed on two AIDS patients, before and after three months of antiretroviral therapy. A decrease of viral load in plasma specimens in association with a change of clonal composition during antiretroviral therapy was observed in both patients during treatment. Before therapy both of the patients had a syncytium inducing (SI) bulk isolate and the majority of the biological clones were characterised as SI. After treatment, the bulk isolates were still SI in both cases, but the majority of biological clones were characterised as non-syncytium inducing (NSI). These results suggest that HIV clonal composition and relative phenotypic pattern undergo different changes not only during the natural course of HIV infection but also while patients are on antiretroviral combination therapy.
Anti-HIV Agents↗
Comparison of once and twice daily dosing of didanosine in combination with stavudine for the treatment of HIV-1 infection. AI 454-146 Team.
OBJECTIVE: To compare the antiviral activity, safety and tolerability of didanosine dosed once and twice daily when administered in combination with stavudine dosed twice daily in human immunodeficiency virus type 1 (HIV-1)-infected individuals with little or no previous exposure to antiretroviral drugs. DESIGN: Comparative, multicentre, randomized, open-label, short-term study. PATIENTS AND METHODS: Eighty-four HIV-1-infected adults with qualifying baseline CD4 cell counts of 200 to 500 cells/mm3 were included in the study. Of these, 43 patients received once daily didanosine plus twice daily stavudine (group A) and 41 subjects received twice daily didanosine plus twice daily stavudine (group B). The primary efficacy analysis used was the time-averaged difference (TAD) between treatment regimens of variations in plasma HIV-1 RNA levels from baseline over the first 12 weeks of therapy. Plasma HIV-1 RNA levels, CD4 cell counts and adverse events were monitored. RESULTS: At week 12, median HIV-1 RNA variations were -1.18 log10 copies/ml in group A and -0.88 log10 copies/ml in group B. For patients who were followed up to week 24, median variations of HIV-1 RNA levels from baseline were -1.21 log10 copies/ml in group A and -0.78 log10 copies/ml in group B. The TAD between the two treatment groups for variations from baseline plasma HIV-1 RNA levels over the first 12 weeks was 0.10 log10 copies/ml (95% confidence interval, -0.19 to 0.40), indicating equivalence. CONCLUSION: Once daily didanosine plus twice daily stavudine and twice daily didanosine plus twice daily stavudine are equally effective in reducing plasma HIV-1 RNA levels and increasing CD4 cell counts. Both regimens are safe and well tolerated.
Adult↗
Bone metabolism in thalassemia.
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Adolescent↗
Asymmetry of the interhemispheric visuomotor integration in callosal agenesis.
We measured visuomotor responses following the Poffenberger paradigm in an acallosal boy, without other detectable neural defects. In this task crossed and uncrossed RT reflect the time of intra- and interhemispheric integration and the difference (CUD) estimates the interhemispheric transfer time. CUDs in the hemifields were largely asymmetrical in this subject, suggesting that visuomotor processing is extremely lengthened when the right hemisphere (RH) detects the light and the left hemisphere (LH) controls the motor output whereas it is very fast in the opposite direction. This asymmetry, which is present in comparable data available from the literature, may indicate the functional superiority of the LH in controlling the ipsilateral hand, as suggested by recent MRI findings.
Acoustic Stimulation↗
Neurological disorders during HIV-1 infection correlate with viral load in cerebrospinal fluid but not with virus phenotype.
OBJECTIVES: To verify the compartmentalization of HIV-1 within the central nervous system (CNS) and to define whether viral phenotype of HIV-1 isolates from cerebrospinal fluid (CSF) samples and CSF viral load correlate with the presence and type of neurological disorders. METHODS: A total of 33 HIV-1-infected patients with and without neurological disorders were included in the study. HIV-1 isolation from paired CSF and peripheral blood mononuclear cell (PBMC) samples was attempted by a standard cocultivation technique; the biological phenotype of HIV-1 isolates was assessed by the MT-2 cell assay. CSF and plasma HIV-RNA levels were measured by a quantitative reverse transcripase-polymerase chain reaction. RESULTS: The rate of HIV-1 isolation from CSF and PBMC was 66% (22 isolates) and 85% (28 isolates), respectively. Seventeen out of 22 (77%) CSF HIV-1 isolates were characterized as non-syncytium-inducing, and 15 out of 28 (68%) isolates from PBMC were typed as syncytium-inducing (SI). The presence of SI isolates in CSF was limited to patients with HIV-1-, cytomegalovirus- or JC virus-related disorders and was often associated with high levels of HIV-1 RNA in the CSF. DISCUSSION: Our results demonstrate a correlation between high levels of HIV RNA in CSF and the presence of neurological disorders thus indicating a possible role for HIV-1 RNA in the CSF as a biological marker of neurological disease. The finding of viruses with a different phenotype in paired CSF and PBMC indicates that HIV-1 may evolve differently in the brain and in the blood. This suggests compartmentalization of HIV-1 within the CNS.
CD4 Lymphocyte Count↗
Measurement of viral sequences in cerebrospinal fluid of AIDS patients with cerebral white-matter lesions using polymerase chain reaction.
OBJECTIVES: To optimize the use of polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) for the evaluation of central nervous system (CNS) white-matter lesions that along with clinical findings and magnetic resonance imaging (MRI) can allow a definite diagnosis to be made; also to evaluate treatment with zidovudine plus foscarnet. DESIGN AND METHODS: Fifteen AIDS patients with uncertain CNS white-matter lesions were identified. HIV-1 RNA, cytomegalovirus (CMV) and JC virus (JCV) DNA were measured in a total of 29 CSF samples. The results were correlated with clinical and MRI findings and treatment with zidovudine plus foscarnet was evaluated. RESULTS: Four and five out of 15 patients with CMV DNA > or = 1 : 625 and JCV DNA > or = 10(3) copies/microl detected in the CSF were diagnosed with CMV and progressive multifocal leukoencephalopathy (PML), respectively. Six patients who were CMV/JCV-negative with the highest levels of HIV RNA (median, 6.87 log10 copies/ml) in CSF were considered as having HIV-1 encephalitis. Neurological symptoms were non-supportive for diagnosis as was MRI in 11 out of 15 patients. Nine patients completed a 21-day course of zidovudine plus foscarnet. HIV RNA decreased irrespective of neurological diagnosis. All three HIV-1 encephalitis patients and two out of three patients with CMV leukoencephalopathy improved. In these two latter patients, relief of clinical symptoms coincided with decreased CMV DNA. JCV DNA remained unchanged and all three PML patients deteriorated. CONCLUSIONS: Measurement of CSF viral sequences supports the diagnosis of CNS white-matter lesions in AIDS patients. While effective therapy for PML remains elusive, treatment including zidovudine plus foscarnet may be a promising option for HIV-1 and CMV-related manifestations.
AIDS Dementia Complex↗
Determination of fecal fat concentration by near infrared spectrometry for the screening of pancreatic steatorrhea.
CONCLUSIONS: Near infrared reflectance analysis (NIRA) is a useful test for diagnosing fat malabsorption. Three-day stool collection and determination of fecal fat output are recommended. The measurement of fat concentration on spot samples may be of some use only in screening malabsorption of pancreatic origin; moreover, it does not discriminate between steatorrhea resulting from pancreatic insufficiency and that caused by gastrointestinal disorders. BACKGROUND: NIRA has been proposed as an accurate method for the determination of fecal fat excretion. The aim of this study was to ascertain whether utilization of this technique to measure fat concentration in spot samples of feces is useful in screening for malabsorption. METHODS: Twenty-five patients with chronic pancreatic disease and 95 with other digestive disorders were studied. In all patients, fecal fat assay with NIRA was performed on three different samples from each daily stool collection for 3 d. In 14 patients with pancreatic disease and 21 with gastrointestinal disorders, a colorimetric assay for fecal fat was performed for comparison. RESULTS: When mean 3-d or daily fat fecal output were considered, a strict linear relationship was found between NIRA and the colorimetric method (r = 0.97 and 0.94, respectively). Using fat concentration, the two tests correlated less well (r= 0.74). Fat concentration was significantly higher in pancreatic than in nonpancreatic steatorrhea, even though values overlapped widely, and thus discrimination was not possible. The diagnostic efficiency of fat concentration for pancreatic and nonpancreatic steatorrhea was 72 and 61%, respectively.
Adolescent↗
Bone mass and metabolism in Whipple's disease: the role of hypogonadism.
BACKGROUND: Whipple's disease, like other malabsorption syndromes, ought to predispose to osteopenia. We therefore evaluated bone mass and mineral metabolism in a cohort of patients with this condition. METHODS: Twelve male patients with Whipple's disease and 36 male age-matched healthy subjects took part in the study. None of the patients complained of diarrhea at the time of the study. Bone mineral density at the lumbar and femoral level and serum levels of indices of bone and mineral metabolism and of gonadal function were measured. RESULTS: Bone mineral density at the total femur and femoral neck were significantly lower in patients with Whipple's disease than in healthy volunteers, whereas no significant difference was found at the lumbar level. In patients with Whipple's disease serum levels of type-I collagen teleopeptide (ICTP) and sex-hormone-binding globulin were significantly higher, whereas serum levels of testosterone and luteinizing hormone were significantly lower than in healthy volunteers. Moreover, testosterone correlated significantly (P < 0.05) with lumbar bone mineral density (r(s) = 0.64) and serum ICTP levels (r(s) = -0.63). CONCLUSIONS: In patients with previously treated Whipple's disease and without any current symptoms of malabsorption, bone loss is generally moderate and linked to the presence of hypogonadism.
Bone Density↗
Bone density and metabolism in thalassaemia.
Twenty-seven thalassaemic patients (13 F, 14 M, aged 8.1-14.9 yr), regularly transfused and chelated with desferrioxamine (30-40 mg/kg/day) were studied. Every patient was submitted to auxological evaluations, dual X-ray absorptiometry to measure bone mineral density (BMD), and to the determination of bone metabolic markers of osteoclastic activity (total urinary hydroxylysylpyridinoline crosslinks, carboxyterminal pyridinoline crosslinked telopeptide of type I collagen [ICTP]) and of osteoblastic activity (bone Gla protein [BGP] and carboxyterminal propeptide of type I procollagen [PIPC]). The evaluations were repeated after 1 year, during which 13 patients continued desferrioxamine chelation while 14 underwent deferiprone chelation (75 mg/kg/day in 3 doses). The data demonstrate widespread bone alterations consisting of osteoporosis, growth failure and bone age delay. Lumber spine (L2-L4) BMD areal values (Z score) inversely correlated with age, as did height SDS of both male and female patients, indicating osteoporosis progressing with age in parallel with growth insufficiency. No clear-cut alterations in bone mineral metabolism were found in basal state and after 1 year. Extensive MR imaging studies are needed to define the contribution of residual bone marrow hyperplasia to thalassaemic osteopathy suggested by subtle radiological signs as enlargement of bone marrow cavities with thinning of the cortical bone and abnormalities of the trabecules of spongy bone.
Absorptiometry, Photon↗
Induction of human immunodeficiency virus type 1 replication in human glial cells after proinflammatory cytokines stimulation: effect of IFNgamma, IL1beta, and TNFalpha on differentiation and chemokine production in glial cells.
Although evidence for human immunodeficiency virus 1 (HIV-1) presence in the central nervous system (CNS) of infected patients is well established, the intensity of viral replication within the brain is not usually known. In vitro, human embryonic microglial cells internalized HIV-1 through a CD4-dependent pathway but were not permissive to viral replication. We observed that HIV replication was induced when CNS cell cultures were stimulated for 14 days by a combination of proinflammatory cytokines including IFNgamma, IL1beta, and TNFalpha. After long-term cytokine stimulation, morphologically differentiated glial cells appeared, in which HIV-1 tat antigen was detected after infection. Thus, variations in the stage of maturation/activation of CNS cells under inflammatory conditions probably play a major role in facilitating massive production of HIV-1. We then studied the effect of prolonged cytokine stimulation on the secretion of inflammatory mediators by glial cells. An early increased secretion of prostaglandin F2alpha and chemokines (RANTES>>MIP-1alpha>>MIP-1beta) was observed, due to both microglia and astrocytes. In contrast to persistent PGF2alpha production, an extinction of RANTES and MIP-1beta but not of MIP-1alpha secretion occurred during the 14 days of stimulation and was inversely correlated with the ability of glial cells to replicate HIV-1. The study of the secretory factors produced in response to a persistent inflammation could provide a better understanding of the modulation of HIV replication in glial cells.
Cell Differentiation↗
Biological correlates of HIV-1 heterosexual transmission.
OBJECTIVES: To study the role of HIV-1 biological phenotype, viral load and neutralizing antibodies in male-to-female heterosexual transmission of HIV-1. METHODS: Seven transmitting and seven non-transmitting HIV-1-seropositive heterosexual male index cases were included in the present study. All couples had engaged in unprotected sex for a period of over 1 year. Transmission was defined by the seroconversion of the female sexual partner. Virus isolates were tested in MT-2 cells for replication and syncytia induction. HIV-1 RNA plasma load was measured by the branched DNA technique. Serum neutralizing activity to primary HIV-1 isolates was tested by using peripheral blood mononuclear cells (PBMC) as target cells. RESULTS: Non-transmitting index cases had a lower HIV-1 RNA concentration in plasma than transmitting index cases. Non-transmitting index cases also tended to have serum neutralizing activity with broad specificity and to have viruses with low replicative capacity, as characterized by 50% infectious dose titres in PBMC and by the lack of MT-2 tropism. CONCLUSIONS: The results indicate that plasma viral-RNA load is a marker for transmission. Moreover, an interplay between the host immune response and viral replication may modulate the level of viral load and thereby influence HIV-1 transmission.
Cell Line↗
Senile osteoporosis: pathophysiology and therapeutic perspectives.
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Aged↗
Propeptide of type I procollagen is predictive of posttreatment bone mass gain in adult celiac disease.
BACKGROUND & AIMS: Adult celiac disease is associated with osteopenia, which is not always reversible after gluten-free diet (GFD). A prospective study was conducted to evaluate whether pretreatment indices of bone and mineral metabolism are predictive of the extent of bone mass gain after diet. METHODS: Lumbar and femoral bone mineral density (z-score) and serum levels of parathyroid hormone, 1,25-dihydroxycholecalciferol, COOH-terminal propeptide of type I procollagen (PICP), and COOH-terminal telopeptide of type I collagen (ICTP) were measured in 20 celiac patients at diagnosis and after 2 years of GFD. RESULTS: All patients showed a posttreatment improvement in bone mass and in serum levels of indices of bone and mineral metabolism. Nevertheless, only in 12 of 20 patients was this improvement at least equal to half the SD of the z-score, which equals a gain of at least 5% in bone mass. Pretreatment levels of PICP strictly correlated with the increase in lumbar (r(s) = 0.92; P < 0.001) and femoral z-scores (r(s) = 0.89; P < 0.001). Only in patients with basal PICP above the normal range did the z-score increase after GFD by at least half the SD. CONCLUSIONS: In adult celiac disease, a high rate of osteosynthetic activity before treatment is predictive of the satisfactory recovery of bone mass after GFD.
Absorptiometry, Photon↗